Mapping evidence and identifying risks: A systematic scoping review of meal replacements in type 2 diabetes

Abstract

BACKGROUND

Type 2 diabetes (T2D) is a major health concern globally and its prevalence is expected to continue to escalate. Lifestyle intervention is an integral part of T2D management. Meal replacements are often used as part of lifestyle intervention programs in T2D and weight management programs. There are various trials being carried out to date; however, a thorough review regarding the usage of meal replacement on its types, dosage and associated outcomes and adverse events is still lacking.

AIM

To provide a comprehensive overview on existing studies regarding meal replacement usage among patients with T2D, and map out glycemic and weight-related outcomes along with adverse effects incidences.

METHODS

This scoping review is conducted based on Arksey and O’Malley’s seminal framework for scoping reviews. A systematic search has been done for studies published between January 2020 and January 2024 across six online databases (Cochrane Library, PubMed, Science Direct, Scopus, Web of Science and Ebscohost Discovery) using specific keywords. Two researchers independently assessed the eligibility of the studies and extracted the data. The selected articles and extracted data were reviewed by all researchers.

RESULTS

The initial search resulted in an initial count of 53922 articles from which 133 articles were included in this review after eligibility screening. Included studies were categorized based on meal replacement type into low calorie/energy, low glycemic index, protein-rich, low-fat, diabetes-specific formulas, and combined lifestyle intervention programs. Fifty-nine studies reported improvements on hemoglobin A1c, and 70 studies reported positive changes in weight or BMI after the meal replacement intervention. The combination of meal replacements with education, counseling or structured lifestyle interventions has proved to be effective. Only 13 studies reported occurrence of adverse events related to the intervention. Most of the reported incidents were of mild occurrences with constipation being the most reported adverse event.

CONCLUSION

The results suggest that meal replacements, especially when combined with lifestyle intervention programs and counseling, are an effective and safe strategy in glycemic and weight management among patients with T2D.

Key Words: Scoping review; Meal replacement; Type 2 diabetes; Glycemic management; Weight reduction

Core Tip: This scoping review systematically evaluated meal replacement interventions in type 2 diabetes, focusing on their effects on glycemic and weight management, as well as associated risks. Key findings included significant improvements in hemoglobin A1c and body mass index after meal replacement interventions, with notable efficacy when combined with lifestyle programs. Most reported adverse events were mild. The review categorized existing studies by meal replacement type and dosage, providing comprehensive insights for tailoring interventions in clinical practice. These results emphasize meal replacements as a promising tool in diabetes management, with implications for improving patient outcomes and reducing healthcare burdens.

INTRODUCTION

According to the International Diabetes Foundation, about 451 million individuals across the globe are currently living with type 2 diabetes (T2D), and this figure is projected to rise to 693 million by 2045[1,2]. T2D with suboptimal glycemic management can lead to a series of comorbidities, such as nephropathy, retinopathy, atherosclerosis, hypertension, osteoarthritis, cardiovascular disease and higher mortality risk[3-7]. T2D has also severely affected the quality of life for the patients[8,9].

T2D and its comorbidities progression have led to a heavy burden on economic and healthcare cost[10-14]. Hence, a cost-effective intervention for the management of T2D is essential to reduce the economic burden of T2D on an already straining healthcare sector. Studies have demonstrated that weight loss positively impacts fasting plasma glucose and hemoglobin A1c (HbA1c) levels in individuals with T2D[15]. Glycemic management among patients with T2D has been closely linked to weight and body mass index (BMI)[16]. The American Diabetes Association (ADA) advises a weight reduction of over 5% for individuals with T2D and overweight or obesity[17]. This guideline is reinforced by findings from the DiRECT study, which revealed that 46% of 306 participants who lost up to 15 kg experienced a clinically significant remission of T2D[18].

Meal replacement represents one strategy for weight management. These products, which include pre-packaged or commercially prepared foods and beverages, are designed to substitute one or more regular meals[19]. As a form of medical nutrition therapy, meal replacement is frequently employed in diabetes care and weight management programs due to its convenience and high retention rates. The 2025 Standards of Care in Diabetes by the ADA endorsed the use of short-term meal replacements for individuals with T2D and overweight or obesity, aimed at achieving an energy deficit and facilitating weight loss[17]. Diabetes United Kingdom also stated in their evidence-based nutrition guidelines that total diet replacement plans providing 800-1200 kcal were effective for weight loss in T2D[20]. Similarly, Diabetes Canada Clinical Practice Guidelines also suggested that partial meal replacement replacing one or two meals could be used for patients with diabetes undergoing weight loss programs[21]. Meal replacement is also recommended by the Malaysia Clinical Practice Guidelines 2020 and the Malaysian Dietitians Association for weight loss and weight maintenance in patients with T2D[22,23].

Numerous trials on meal replacements are ongoing; however, a comprehensive review focusing on their types, compositions, dosages, and delivery methods remains insufficient. This scoping review aimed to consolidate existing research on meal replacements for managing T2D. We explored the types of meal replacements available for adults with T2D and evaluated their respective impacts on glucose regulation/HbA1c, weight loss, and other health outcomes. Additionally, potential risks or side effects associated with these meal replacements were identified. The findings were systematically organized by categorizing and summarizing the reviewed studies. The specific objectives of this scoping review included the following: (1) To present a comprehensive overview of existing research on the use of self-administered meal replacements in adult patients with T2D; (2) To systematically map the effects of self-administered meal replacements on specific parameters, including HbA1c levels, glucose regulation, and weight reduction in participants; and (3) To identify and categorize the adverse effects associated with the use of self-administered meal replacements among adults with T2D.

MATERIALS AND METHODS

A previously published study protocol outlined the search strategy and provided detailed explanations of all methodological steps[24]. This scoping review adopted the methodological framework proposed by Arksey and O’Malley[25]. Reporting of the review followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA) checklist, which is available in Supplementary material[26].

The key stages in conducting this scoping review included: (1) Formulating the research question; (2) Identifying relevant studies; (3) Selecting studies for inclusion; (4) Extracting and organizing information from the selected studies; (5) Synthesizing and reporting the findings; and (6) Engaging in consultations with stakeholders.

Stage 1: Identifying research questions

(1) What are the various types, compositions, dosages, delivery methods, and durations of meal replacement plans utilized for the management of patients with T2D? (2) How do meal replacements affect glycemic management (HbA1c), weight reduction, and other health parameters in patients with T2D?; and (3) What adverse effects, if any, are reported by patients with T2D using meal replacements?

Stage 2: Identifying relevant studies

A systematic and extensive search was conducted for studies published between January 2000 and January 2024. In our previously published protocol, the search period was limited to January 2000 through August 2020[24]. We updated the search up to January 2024 to include more recent studies. The detailed search strategy is available in our previously published protocol[24]. Keywords and search terms were developed using the PICO framework, with synonyms identified for the key terms. These keywords (e.g., meal replacement, T2D, glycemic management, weight reduction, and risks) and their synonyms were combined to create multiple search strings. These strings were applied by the research team across various databases to capture all relevant resources (Supplementary material).

The study identification process was conducted across six online databases: Cochrane Library, PubMed, Science Direct, Scopus, Web of Science, and EBSCOhost Discovery. Additionally, manual searches were performed on reference lists of included studies and reviews to enhance coverage. Review articles were excluded from our analysis. Two independent researchers, Lew LC and Mat Ludin AF, carried out the searches simultaneously, employing a comprehensive search strategy.

Stage 3: Selection of studies to be included

Studies were selected based on predefined inclusion and exclusion criteria as detailed in our previously published protocol paper. The screening and selection process was conducted in three steps.

In the first step, two researchers, Lew LC and Mat Ludin AF, reviewed all titles retrieved from the database searches. All articles that involved meal replacements and patients with T2D were considered.

In the second step, the researchers independently assessed the selected titles and abstracts from step one to identify studies potentially relevant to the objectives.

In the third step, the researchers independently reviewed the full-text articles identified in step two. If full-text articles were not accessible online, they were obtained through the university library. Each full-text article was thoroughly examined to ensure alignment with the study objectives. Regular meetings were held among all researchers to discuss results and address any disagreements. The PRISMA flow chart was utilized to guide and document the study selection process.

Stage 4: Charting of data from the selected studies

Two researchers, Lew LC and Mat Ludin AF, carried out data extraction and charting. The primary outcomes extracted included the types and dosage of meal replacements and their effects on HbA1c, glucose levels, and weight reduction. Additionally, the side effects of meal replacements were recorded. Other significant findings were documented as 'other health status'. Other researchers, Shahar S, Abdul Manaf Z and Mohd Tohit N subsequently reviewed the extracted data for accuracy. Any discrepancies were addressed and resolved during group discussions.

Stage 5: Collating, summarizing, and reporting of results

Following data extraction, the information was categorized and summarized based on the types of meal replacements, including low-calorie/energy meal replacements, low glycemic index (GI) meal replacements, diabetes-specific formulas, protein-rich meal replacements, low-fat meal replacements, and combined meal replacements integrated with lifestyle intervention programs.

The complete data is presented in the results section and detailed in Supplementary material.

Patient and public involvement

This scoping review was exclusively based on literature and did not involve any patient or public participation.

RESULTS

Study selection and characteristics

A total of 53922 articles were obtained from our search from six different databases. After removing the duplicates and screening through the titles, most of the records searched were excluded due to our overinclusive search strategy, leaving only 1326 articles to be screened subsequently for their abstract. Of the abstract screened, 286 records were included for in-depth full text review. Finally, 133 articles were selected to be included in the review. The PRISMA flow diagram in Figure 1 outlines the search and selection procedures implemented during the systematic literature search for this scoping review.

Figure 1 PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only. T2DM: Type 2 diabetes mellitus.

The included publications (n = 133) in the data extraction were published between the year 2001 to 2024. Most of the studies were published after year 2010 (n = 106) with only 27 studies published by 2010. Among the 114 studies selected, 27 studies were from the Look Ahead study, three were from the WAIT study, four were from the DiRECT study, two were from the Malaysian tDNA study, five were from the POWER study, and two were from the Diadem study. We have combined and summarized the articles of each study under one entry in the results section for easier interpretation. Hence, there were 96 articles presented in the table. The 133 studies selected involved 49 studies from the United States, involving 3301 participants; 47 studies from Europe, involving 2872 participants; 22 studies from Asia, involving 1401 participants; four studies from Canada, involving 514 participants; one study from Brazil, involving 34 participants and 10 studies from Australia and New Zealand, involving 416 participants. Detailed distribution of studies according to the geographical location is as shown in Table 1.

Table 1 Distribution of studies and participants according to geographical location.

Country	Number of studies	Participants in meal replacement arm (n)	Ref.
Asia
China	7	465	[33,37,44,47,86,103,104]
India	4	303	[63,82,92,93]
Japan	1	119	[91]
Malaysia	3	193	[24,45,141]
Singapore	1	19	[85]
Indonesia	1	30	[117]
Taiwan	1	30	[46]
Thailand	2	172	[39,118]
Qatar	2	70	[40]
Oceania
Australia	9	396	[36,52,55,56,61,90,95,106,116]
New Zealand	1	20	[70]
America
Canada	4	514	[48,54,62,94]
United States	49	3301	[30,34,38,43,49,50,72-76,80,84,88,89,96,101,107,115,121,122]
Brazil	1	34	[100]
Europe
Czech Republic	1	22	[102]
Denmark	1	11	[83]
Germany	8	700	[57,64-68,81,120]
Greece	1	43	[59]
Italy	3	77	[32,41,97]
Netherlands	8	147	[28,31,42,87]
Spain	1	17	[29]
Sweden	2	392	[109,114]
Ireland	1	20	[113]
United Kingdom	21	1443	[18,35,51,58,60,69,71,77-79,99,105,106,108,110-112,119]

Intervention design and delivery mode

Among the studies included, 116 completed intervention studies while another 17 were study protocols. Among the intervention studies, most studies were randomized-controlled trials (RCT). The included studies comprised a total of 8543 participants undergoing meal replacement intervention. Only one study protocol did not report the number of participants. T2D was an inclusion criterion for all the included studies while overweight and obesity were an inclusion criterion for 62.4% of the studies (n = 83).

Majority of the participants were recruited from clinical establishments which included hospitals, clinics, lifestyle intervention centers, university research centers and other healthcare facilities while approximately 7% of participants (n = 601) were recruited from community settings. The age of the participants ranged from 18 years old to approximately 75 years old, with majority being in the 50-60 years age group, which is in line with the higher prevalence of T2D in the group aged 50 years and above based on the data from the Global Burden of Disease[27].

More than 60% of the included studies incorporated diet education or counseling sessions delivered by trained personnel. Specifically, 33 studies involved a research dietitian, four involved a physician, and 15 utilized both a physician and a dietitian. Additionally, two studies worked with nurses, three involved a combination of dietitians and nurses, five worked with trained counselors or diabetes educators, and a study reported the involvement of a pharmacist. The duration of these sessions typically ranged from 15 minutes to an hour, although one study reported a 90-minute session and another extended to 2 hours. The session most often occurred at baseline and continued weekly or biweekly throughout the intervention.

Health outcomes measured

Clinical outcomes extracted and assessed included HbA1c, glucose levels, body weight/BMI, lipid profiles and some other indicators related to glycemic management, such as insulin levels if reported.

HbA1c was measured in 60 of the studies. Of these, 59 studies (98.3%) reported improvements in patient’s HbA1c levels. For example, a study by Lean et al[18] demonstrated a reduction in mean HbA1c levels of -0.9% among 149 intervention group participants compared to baseline after 12 months of meal replacement intervention. Only one study showed no significant changes in HbA1c levels[28].

Glucose level was measured in 48 of the included studies. Among them, 42 studies showed improvements in glucose levels. The reduction in glucose levels was often accompanied by a reduction in HbA1c levels among participants in most of the studies. Some studies (n = 6) have reported no changes in fasting glucose levels after meal replacement interventions[29-34].

Changes in weight or BMI were the most common outcome measured in 71 of the studies; 70 of them reported positive improvements while only one of them reported no changes after intervention[28].

Lipid profiles, such as cholesterol and high-density lipoprotein (HDL) levels, were evaluated as outcome measures in 42 studies. Among these, 36 studies reported positive effects, while six observed no significant changes[28,29,35-38]. One study noted an increase in triglycerides[39] and another reported elevated total cholesterol and low-density lipoprotein (LDL) levels[40].

Meal replacement intervention strategies

Meal replacement interventions were grouped into low calorie/energy, low GI, protein rich, low fat meal replacements, diabetes specific formulas as well as combined meal replacements with lifestyle intervention programs. There was a series of commercially available meal replacements used in the trials, including Glucerna SR (13 trials)[28,37,38,41-50], Optifast (14 trials)[36,50-62], Almased Vitalkost (6 trials)[63-68], Cambridge Weight Plan (4 trials)[35,40,69,70], Slimfast (5 trials)[50,71-74], HMR (3 trials)[50,75,76], Counterweight Pro 800 (4 trials)[18,77-79], ONCE-PRO[39], Medifast[80], Modifast[81], Prototal Whey[82], Nutriletts[83], Nutrimed[84], Kicstart[85], Maide Technology co[86], Prodimed[87], Nutrisystem D[88,89], Probiotec Formula WL[90], Enerzona[29], Microdiet[91], Glucaeffect[32], Prohance D[92,93], Diasip[31], Ultra Glucose Control[38], Ideal Protein[94], Quaker Oats[38], KicStartä[95], BOOST Glucose Control[96], Therascience[97], Metabolic Sauver[98], LighterLife[99], and Nutren Control[100].

Table 2 provides comprehensive information on meal replacement types and dosage for the included studies. Detailed mapping of each study with outcome is presented in Table 3.

Table 2 Types, composition, dosage, and duration of meal replacement intervention for type 2 diabetes.

Ref.	Country	Trial type & setting	Setting	Meal replacement arm (n)	Meal replacement type	Dosage/calorie	Combination	Length of intervention/follow up
Low calorie/energy MR (n = 35)
Rothberg et al[75]	United States	Observational study	Clinical	66	HMR®, Boston, MA, United States	TDR; 160-170 kcal per packet, total 800 kcal per day; > 160 kg additional 160-170 kcal/day per 23 kg	/	12 weeks
Tatti et al[41]	Italy	Non-randomised controlled trial	Clinical	38	Glucerna® SR, Abbott Nutrition	PMR; 206 calories per 230 mL for one main meal; Blend with low calorie frozen yoghurt into 250-270 kcal	/	12 weeks
Steven et al[51]	United Kingdom	Longitudinal study	Clinical	30	Optifast (Nestle Nutrition, Croydon, United Kingdom)	TDR; 3 shakes per day + 240 g non starchy vegetables; total Cal intake 624-700 kcal/day	/	8 weeks VLCD; + 24 weeks wight maintenance phase
Shantha et al[101]	United States	Cohort Study	Clinical	72	Calorie-restricted diet using meal replacements	1000 kcal/day energy deficit; Individualized	Behaviour modification plan; Aerobic and strength training	Individualized 3 months to 1.5 years
Astbury et al[35]	United Kingdom	Randomized controlled trial	Clinical	138	TDR with four formula products daily (LCD) provided by Cambridge Weight Plan United Kingdom	TDR; First 2 weeks, liquid MR. Week 3 onwards MR bars option; Energy intake comprised 810 kcal/day (3389 kJ/day)	/	8 weeks LCD, gradual food reintroduction, weekly behavioural support for 24 weeks - one MR is consumed per day
Baker et al[52];	Australia	Non-randomized case-control trial	Clinical	37	Optifast (Nestle Nutrition, Croydon, United Kingdom)	TDR; 3 sachets daily combined with serving of vegetable once daily (800 kcal/day)	After week 12, 8-week transition phase to calorie restriction diet based on Australian Commonwealth Scientific and Industrial Research Organization Total Wellbeing diet (1350 kcal) for another 4 weeks	12 weeks VLCD + 8 weeks transition to calorie restriction diet + 4 weeks 1350 kcal diet
Bishay[53]	Australia	RCT Protocol	Clinical	Not reported	Optifast (Nestle Nutrition, Croydon, United Kingdom)	TDR; 5-months of complete VLCD (820 kcal/day)	/	32 weeks
Bhatt et al[82]	India	Clinical Audit	Clinical	12	Protein formula (Prototal Whey)	TDR; 1000 kcal/day diet	/	12 weeks
Berk et al[42]	Netherlands	Randomized controlled trial	Clinical	64	Glucerna® SR, Abbott Nutrition	PMR; Replace breakfast and lunch; Light dinner for a combined 750 kcal/day	/	8 weeks + 12 weeks LCD reintroduction (1300 kcal/day)
Shiau et al[54]	Canada	Retrospective cohort study	Clinical	317	OPTIFAST® 900	TDR; 4 MR shakes per day for a total of 900 kcal per day	First 6 months - weekly diet session, behavioural and therapy; Next 6 months - optional monthly support session	BMI > 33 kg/m2 - 12 weeks of full MRs; BMI < 33 kg/m2 - 6 weeks of full MRs with option to increase to up to 12 weeks of full MRs; 5-week transition to maintenance diet
Cinkajzlová et al[102]	Czech Republic	Intervention study	Clinical	22	VLCD	2500 kJ per day	/	/
Taheri et al[40]	Qatar	Non-blinded, randomised controlled, parallel-group trial	Clinical	70	LCD from Cambridge Weight Plan	800 kcal; First 12 weeks: TDR supplemented by low-fat milk; Month 4 to month 6: PMR; Gradual introduction to three meal per day eating pattern	Individual dietetic and activity appointments. Unsupervised physical activity of at least 150 minutes per week	PHASE 1: 12 weeks LED + physical activity; PHASE 2: 12 weeks partial LED + physical activity; PHASE 3: 6 months own food, physical activity, and lifestyle change. PHASE 4: 12 months follow-up
Harder et al[83]	Denmark	Single arm study	Clinical	11	Nutriletts (NutriPharma, Oslo, Norway)	TDR; 850 kcal/day	/	8 weeks
Friedman et al[84]	United States	Proof-of-concept pilot study	Clinical	6	Nutrimed (Robard Corporation, Mount Laurel, NJ, United States)	PMR; 800 kcal/day	/	12 weeks
Lean and Leslie[77]	United Kingdom	RCT protocol	Clinical	Total N = 25	Counterweight Pro 800	TDR; Initial Total Diet Replacement phase (0-12 weeks); 825-853 kcal/day	Counter weight-Plus’ weight management programme; Structured food reintroduction (12-20 weeks).; -Replacing TDR with meals which contain 30% of energy from fat	20 weeks with initial 12 weeks TDR
Wong et al[103]	China	Randomized, non-blinded, single center trial	Clinical	Total N = 37	LED	PMR; Replace at least one meal with less than 300 kcal	/	24 weeks
Leader et al[55]	Australia	RCT	Clinical	36	Optifast VR	PMR; 1 or 2 PMR per day	/	12 months
Overl et al[104]	China	Conference paper; RCT	NA	Total N = 10	MR shakes	Three meal replacement shakes (600 kcal/day) for two 24-hour periods/week	/	12 weeks
Gulsin et al[69]	United Kingdom	Single-center, prospective, randomized, open-label, blinded end point trial with a nested case-control study	Clinical	24	Low energy MRP from Cambridge Weight Plan	TDR approximately 810 kcal/day (Cambridge Weight Plan)	/	12 weeks
Farrer and Golley[36]	Australia	Non-randomized intervention	Clinical	19	Optifast VLCD programme	Three phases of 4 weeks each: Intensive (3 Optifast VLCD per day, < 3360 kJ/day), Transition (2 Optifast VLCD per day, approximately 5040 kJ/day) and Maintenance (1 Optifast VLCD per day, approximately 5040 kJ/day); 12th week: Full normal meals were resumed to meet energy deficit requirements of 50% total energy	Traditional diabetes and weight management education	12 weeks
Sumithran and Proietto[56]	Australia	Case study	Clinical	1	Optifast VLCD	TDR; 5 months VLCD 3 times a day (1908 kJ); Transition phase 7 months: Two VLCD meals per day and one low fat meal per day	Daily exercise program; Weight control clinic	12 months
Rolland et al[105]	United Kingdom	Case study	Community	355	VLCD in the form of food packs (soups, shakes, textured meals and bars)	TDR; 550 kcal daily	Commercial weight-management programme (Lighter Life Total); Group support; Cognitive behaviour therapy	12 weeks
Dhindsa et al[71]	United Kingdom	Intervention	Clinical	44	VLCD Slimfast, liquid MR	PMR; 3 Slimfast MR per day; 750 cal	Follow-up phase (week 8 to week 52) with a standard low-calorie weight-maintenance diet	(1) 8 weeks of VLCD therapy; and (2) Follow-up phase (week 8 to week 52) with a standard low-calorie weight-maintenance diet
Khoo et al[85]	Singapore	Randomized Trial	Clinical	19	Liquid meal replacement (Kicstart, Pharmacy Health Solutions, Sydney, Australia)	PMR; Maximum 450 kcal, 0.8 g/kg ideal body weight of protein and one other small meal, for a total of approximately 900 kcal/day for 8 weeks	Switch to or continue high protein diet for the remaining 44 weeks	8 weeks LCD/52 weeks
Moriconi et al[97]	Italy	Retrospective study	Clinical	15	Very-low-calorie ketogenic diet (VLCKD) (Therascience, New Penta SRL or Pronokal Group)	First phase (45 days) TEI was < 800 kcal with 4/5 MR per day. Second phase (45 days), one and subsequently two replacement meals were replaced with conventional food	Caloric intake gradually increases; Full carb reintroduction - 6 months	Phase 1 - 45 days; Phase 2 - 45 days; Phase 3 - until 12 months
Tang and Lin[86]	China	RCT	Clinical	50	Fasting-mimicking diet (FMD) MR (Maide Technology Co., Ltd., Wuhan, China)	PMR; FMD MR from Monday to Friday in the second week of a month. Eat normally for the rest of the month. Energy for first day and the second to fifth days was 1196 and 805 kcal respectively	/	First 3 months - MR; Last month - normal diet
Maher et al[106]	Ireland	Case study	Clinical	1	Low-energy liquid diet	TDR; 1012 kcal per day with 2.2 L of semi-skimmed milk	/	8 weeks LELD; + 16 weeks of phased reintroduction of normal diet
Nori Janosz et al[34]	United States	Retrospective chart review	Clinical	33	LCD MR	PMR; 1000-1200 kcal/day	Behavioural treatment plan	At least 4 weeks
Storck et al[57]	Germany	Prospective, interventional study	Clinical	36	OPTIFAST® II Short program, Nestlé Health Science, Germany)	TDR; 5 sachets per day of 800 kcal for 6 weeks. 4-week refeeding phase.; Last 5 weeks, energy intake will be gradually increased to between 1200 and 1500 kcal	Standardized weight-loss program (OPTIFAST® II Short program, Nestlé Health Science, Germany); Weekly visit for exercise training. Diet counseling	12 weeks
Schwasinger-Schmidt et al[107]	United States	Retrospective analysis	Community	44	LCD in form of shakes, soups, cereal, and entrees	TDR; Consume at least five meal replacements with a minimum of 800 kcal per day	Weekly behavioural education classes	12 weeks
Steven and Taylor[58]	United Kingdom	Intervention study	Clinical	30	VLCD liquid MR (Optifast)	TDR; Replaced all meals with Optifast 624 kcal/day	Discontinued all diabetic medications	8 weeks
Redmon et al[72]	United States	RCT	Clinical	30	LCD MR (meal shakes or meal bars) (Slim Fast Foods Company)	PMR; Repetitive intermittent LCD weeks: LCD of 900-1300 kcal per day (220 kcal/serving, four to six servings daily) for 7 consecutive days every 2 months; On normal days, use one MR and one snack bar (120 kcal/snack bar) daily to replace one usual meal and snack to reach 500 to 1000 kcal per day reduction goal	Combination therapy group; Individual counseling by a registered dietitian; Individualized diet of 500-1000 kcal reduction in daily energy; Individualized exercise prescription	12 months
Lips et al[87]	Netherlands	Controlled nonrandomized observational trial	Clinical	12	Commercially available Prodimed (Prodimed Benelux BV, Val-Kenswaard, The Netherlands)	TDR; 4-5 sachets a day with 90 kcal each sachet, average 600 kcal/day	/	3 weeks
Elizabeth O Beale[76]	United States	RCT protocol	Clinical	15	TDR first 3 months; PMR 3-6 months; HMR70 Plus products; HMR Boston, MA, United States	Phase 1: TDR 3-months 1200-1400 cal diet. Phase 2: Regular meals and 1 MR/day. Phase 3: 6-month weight loss maintenance period with 1 MR/day	Usual care at Roybal Diabetes Management Clinic	12 months
Abi-Chahine et al[108]	United Kingdom	Abstract for poster presentation for a person-centred intervention study	Community	23	TDR	TDR of 800 kcal daily supplementation	Food reintroduction after 12 weeks; Culturally sensitive diet and lifestyle support through 26 e-learning modules	24 weeks
Rafey et al[113]	Ireland	Prospective observational cohort study	Clinical	20	Milk-based LELD	TDR; Week 1-8: Approximately 1200 kcal/day, or 130 g of carbohydrates and 40 g of fat intake per day. Week 9-16: Gradual reintroduction of low calorie meals.; Week 17-24: Stopped milk replacement and start fully isocaloric meal plan	/	24 weeks
Reynolds[70]	New Zealand	RCT protocol	Clinical	20	Cambridge Weight Plan products (VLED)	TDR; Consumption of 3-4 meal replacements per day providing approximately 3600 kJ/day	Structured programme with monthly visits for long-term weight loss maintenance	12 weeks
Scragg et al[112]	United Kingdom	RCT protocol	Clinical	254	Low-energy low-carbohydrate diet	TDR; 800-1000 kcal with a maximum of 40-60 g carbohydrate/day, compared to usual intake of 200-250 g	/	6 months
Tsompanaki et al[111]	United Kingdom	RCT protocol	Community	28	TDR with LED	TDR; LED with package of soups, shakes, bars (4 per day providing approximately 850 kcal/day) for first 12 weeks	Stepped food reintroduction starting from 12th weeks and weight maintenance phase	12 months
Shirmann[110]	United Kingdom	RCT protocol	Clinical	36	TDR with Low-calorie Diet Programme	TDR; approximately 850 cal per day through four TDR products daily for 12 weeks; Followed by a 6-week food reintroduction period and weight maintenance support for 8 months		12 weeks
Hocking et al[61]	United Kingdom	Single arm intervention trial	Clinical	155	TDR with LED; Optifast; Nestlé Health Science	TDR; 3 MRP per day (800 kcal per day). If BMI more than 40, 950 kcal per day	Dieitian visits every 2-4 weeks	13-week TDR; 8 weeks structured food reintroduction; 31-week supported weight maintainence
Ekberg[109]	Sweden	RCT Protocol	Not stated	286	Low Carb or low calorie diet	Not stated	/	15 months
Low glycemic index MR (n = 5)
Stenvers et al[28]	Netherlands	Randomized, controlled, cross over trial	Clinical	29	Glucerna SR (Abbott Nutrition)	PMR; Baseline breakfast intake mean 292 kcal	/	12 weeks
Foster et al[88]	United States	Randomized controlled trial	Clinical	50	Pre-packaged, Portion Controlled Diet (Nutrisystem D, Fort Washington, PA, United States)	PMR; Women approximately 1250 and men 1550 kcal per day, with approximately 55% of total energy from the packaged foods and 45% from supplemental grocery items	/	6 months
Boonyavarakul et al[39]	Thailand	Randomized controlled trial	Clinical	60	ONCE-PRO	PMR; Replace one meal per day to provide 30% of energy intake; Aim: 25-30 kcal/kg/day	/	12 weeks
Li et al[33]	China	randomized, open label, interventional study	Clinical	47	Multi-nutrient powdered supplements (LEHEL Company, Guangzhou, China)	PMR; Provides 346 kcal energy in place of breakfast	Diabetic health education organized by nutritionists every 2 weeks	12 weeks
Eliana and Pranoto[117]	Indonesia	Randomized, controlled, crossover, open-labelled study	Clinical	30	Carbohydrate mix-fortified liquid meal replacement nutrition (LMRN)	TDR; 4008 kcal	/	4 days × 2 (crossover)
Santen et al[89]	United States	Intervention Pilot study	Clinical	11	TDR with Nutrisystem®D® Meal Replacements, Nutrisystem Inc.	TDR; 1450 to 1550 kcal/day for men; 1200 to 1250 kcal/day for women	Telcare with glucometer, weighing scale and cloud data assessment.; Education sessions	6 months
Otten[114]	Sweden	RCT Protocol	Clinical	106	TDR	TDR for 850 kcal/day	Cognitive behavioural therapy programs through face to face or ehealth application	Total diet replacement for 3 months. Weight maintenance for 21 months
Anyiam et al[99]	United Kingdom	RT	Clinical	18	TDR VLCD; LighterLife® total meal replacement	TDR VLCD with less than 800 kilocalories per day	/	12 weeks
De Freitas et al[115]	United States	Case study	Clinical	1	TDR VLCD with a formula liquid diet meal replacement	TDR 800 kcal/day; Twelve weeks of VLCD were followed by 4 weeks of low-calorie diet (incorporating 3 meal replacements and 1 meal with ad libitum non-starchy vegetables)	/	16 weeks
Khoo et al[116]	AUS	Retrospective cohort study	Clinical	51	PMR with LCD	PMR Two meal replacement shakes plus a healthy meal	/	3 months PMR + 21 months reduced calorie meal
Diabetes Specific Formulas (n = 16)
Belcaro et al[32]	Italy	Single blinded RCT	Clinical	24	Glucaffect™ (Reliv Inc., Chesterfield, MO, United States)	PMR; Substitute up to two meals a day for 6 days a week. Dinner following regular choices	Personal Exercise Program with 60 minutes each day	8 weeks
Fonda et al[43]	United States	Prospective, 3-way, cross-over design	Clinical	18	Glucerna Weight Loss Shake, Slim-Fast Shake, and Ensure with Fiber Shake	Subjects consumed the meal replacement; beverages after an overnight fast, in random sequence on; different weeks, 1 week apart	/	1 week
Garvey et al[119]	United Kingdom	Multi-center, single arm, unblinded study	Clinical	147	/	PMR; Two meal replacement shakes and snack bars daily	Diet and lifestyle counseling	12 weeks + 12 weeks sustainability
Sun et al[37]	China	Unblinded, randomized, controlled clinical trial	Clinical	100	Glucerna SR (Abbot Nutrition)	PMR; Replace breakfast, providing 200 kcal	Weekly sessions on: Diet consultation; Review of blood glucose measurements	24 weeks
Peng et al[44]	China	RCT	Clinical	62	Glucerna SR (Abbot Nutrition)	PMR; Replacing breakfast providing 220.5 kcal	Lifestyle education; Individualized meal plan	4 weeks
Chee et al[45]	Malaysia	RCT	Clinical	115	Glucerna SR (Abbot Nutrition)	PMR; Structured low-calorie meal plan - 1200 or 1500 kcal/day; Normal foods + one or two diabetes-specific formula servings	tDNA group receives physical activity at least 150 minutes/week; Education using tDNA toolkit: Flipchart on healthy eating, 14-day meal plans, information on physical activity; Subgroup receives motivational interviewing or conventional interviewing	6 + 6 months follow-up
Patel[92]	India	RCT Protocol	Clinical	100	Prohance D Vanilla Flavour (Nutraveutical Product)	PMR; Once a day	/	12 weeks
Hwu[46]	Taiwan	RCT protocol	Clinical	30	Glucerna SR (Abbot Nutrition)	PMR; To replace one meal (breakfast) and one pre-sleep snack for 24 weeks	Diet plan with 500-800 kcal/day less than their estimated daily maintenance energy requirement	24 weeks
Bao[47]	China	Single-centre, Randomized, Open-label, Parallel Group Study Protocol	Clinical	66	Glucerna SR (Abbot Nutrition)	To replace breakfast	/	4 weeks
Lansink et al[31]	Netherlands	Randomized, controlled, double-blind, parallel-group study	Clinical	22	Diasip® (Nutricia N.V., Zoetermeer, The Netherlands)	PMR; Two 200 mL portions (200 kcal per portion) per day for 4 weeks, one for breakfast and one for snack in the afternoon or evening	/	4 weeks
Mottalib et al[30]	United States	A prospective, randomized, three-arm study	Clinical	72	DSNF	PMR; Group B and C - hypocaloric dietary plan (1500 kcal/day for women, 1800 kcal/day for men) with a commercially available DSNF (220 kcal/serving) 1-3 times per day	/	16 weeks
Otto et al[48]	Canada	Retrospective cohort study	Clinical	47	Glucerna SR (Abbot Nutrition)	PMR; 2 cans of Glucerna per day (230 kcal/serving as part of a 1200 to 1400 kcal diet)	/	At least 3 months
Yip et al[73]	United States	RCT	Clinical	41	Liquid MR preparation containing lactose, fructose, and sucrose (Slim-Fast; MR1); Liquid MR in which sucrose and fructose were replaced by nonsugar-containing glucose oligosaccharides (sugar-free Slim-Fast; MR2)	MR1 (Slim-Fast Foods, New York, NY, United States): 11 g lactose, 13 g fructose, 8.5 g sucrose, and 14 g protein. MR2: Identical to MR1, fructose and sucrose were replaced with equivalent levels of maltodextrins. (250 kcal each); Replaced their three meals with MRs for the first 5 days. Replaced two meals for remainder of the study	/	12 weeks
Mottalib et al[38]	United States	Cross-over, three-way and open-label clinical study	Clinical	22	Three types of meal replacement served on each visit on breakfast: Glucerna (Abbott Nutrition Inc., Columbus, OH, United States); Ultra Glucose Control (Metagenics Inc., Aliso Viejo, CA, United States); OM (Quaker Oats Co., Chicago, IL, United States)	PMR for breakfast; 200 kcal/meal	/	Three visits with crossover of different MR
Cheskin et al[80]	United States	Controlled clinical trial	Community	54	Medifast Plus for Diabetics (Medifast, Inc, Owings Mills, MD, United States)	PMR; 25% of energy calorie deficit at weight-loss-phase diet; 10% calorie deficit at weight-maintenance-phase diet. PCD group received 50% to 60% of their prescribed calories from meal replacements	An initial 34-week weight loss period, then PCD participants were rerandomized for 52-week maintenance phase to either 26 weeks of PCD followed by 26 weeks of Standard Diet (PCD1) or vice versa (PCD2)	34-week weight loss period and 52-week maintenance phase (86 weeks)
Mustad et al[49]	United States	Randomized, open-label, three-group parallel study design	Clinical	49	Glucerna Hunger Smart (Abbott Nutrition, Columbus, OH, United Sates)	PMR; One meal supplies 180 kcal. DSNS breakfast and afternoon snack (Bkfst/AS); DSNS breakfast and bedtime snack (Bkfst/PBS); Self-selected diets for 7 days, then MR for 7 days	/	7 SSD + 7 days MR
Lew et al[98]	Malaysia	RCT Protocol	Clinical	78	PMR with Diabetes specific meal replacement - Metabolic Sauver, Powerlife (M) Sdn Bhd, Kuala Lumpur, Malaysia	PMR for 5 days a week replacing 1 meal per day, providing 327 kcal per comsumption	Dietary Consultation	12 weeks intervention + 12 weeks follow up
Wichansawakun[118]	Thailand	RCT Protocol	Not stated	76	PMR with Diabetes specific meal replacement	Replace 1 meal per day based on weight based calculation at 25-30 kcal of energy per ideal body weight per day, and the ratio of carbohydrates to protein to fat is 45-50:20:30-35 of total energy	/	12 weeks
Dharmalingam et al[93]	India	RCT	Clinical	71	PMR with DSNS (Prohance-D® Vanilla flavored powder); (Sun Pharmaceutical Industries Limited, Mumbai, India)	One serving of DSNS used as breakfast/evening snack replacement, providing 16.8% of the recommended daily allowance (RDA) of protein, 454 kcal energy	Oviva Diabetes Remission Insulin (ODR-I) programme: Expert dietitian coaching; Oviva app (with a 12-month weight prediction chart); Capilar Blood Glucose meters; BodyTrace weight scales	12 weeks
Zagury et al[100]	Brazil	Randomized control crossover trial	Clinical	34	Glycemia targeted specialized supplement PMR; Nutren Control®, Nestle	Replaced breakfast to provide 208 kcal	/	7 days
Protein rich MR (n = 13)
Keogh and Clifton[90]	Australia	Randomized controlled trial	Community	60	Probiotec Formula WL (Probiotec Limited, Laverton North, VIC, Australia 3026)	PMR; 2 MR (880 kJ each) and low-fat evening meal per day first 12 weeks + at least 5 serves of fruit and vegetables/day (total approximately 5000 kJ); 1 MR for further 12 weeks	/	24 weeks
Navas-Carretero et al[29]	Spain	Single group, sequential, longitudinal design	Clinical	17	4 weeks Structured meal replacements: Breakfast, morning snack and afternoon snack, were exchanged by specific products, with a moderately high protein content and low glycemic index (55); Enerzona© (Equipe Enervit)	TDR; approximately 1800 kcal	/	4 + 4 weeks
Manjunath[63]	India	Randomized, Parallel Group, Multiple Arm Trial Protocol	Clinical	120	Almased Soya protein powder with yogurt	PMR; First 6 months, Almased substituting one major meal/day; Dosage will be defined individually according to body weight. Next 6 months, Almased (50 g/day) added to the diet before one meal	/	6 + 6 months follow-up
Kempf et al[64]	Germany	Proof of principle study	Clinical	22	Almased-Vitalkost; Almased-Wellness-GmbH, Bienenbüttel, Germany	First week, breakfast, lunch and dinner replaced with Almased (50 g per meal = 150 g per day = 2223 kJ) + 45 g oil (1717 kJ) + 750 mL vegetable juice (544 kJ), Total 4903 kJ per day. 2-4 week: Breakfast and dinner (1465 kJ) + regular lunch (2093 kJ) + 45 g oil, total 4600-5300 kJ; 5-12 week, only dinner is replaced with 50 g Almased	/	12 weeks
Kempf et al[65]	Germany	RCT	Clinical	Strict diet regime N = 37; Moderate group N = 43	Almased®, Almased-Wellness-GmbH, Germany	PMR; Strict diet group replaced three meals in week 1, two meals in weeks 2-4 and one meal in weeks 5-12 with 1 g PMR (Almased®) per kg normal body weight.; Moderate group replaced two meals in weeks 1-4 and one meal in weeks 5-12	/	12 weeks + 9 months follow up
Kempf et al[120]	Germany	Conference paper; RCT	Clinical	55	Protein-rich meal replacement	PMR	/	12 weeks
Martin et al[66]	Germany	RCT	Clinical	Stringent diet regime (n = 40); moderate diet regime (n = 37)	Almased-Vitalkost, Almased Wellness GmbH, Bienenbüttel, Germany	1st week: Replaced 3 main meals by 50 g PMR = 1100 kcal/day; 2-4th week: 2 meals were replaced, and a protein-rich lunch was allowed; 5-12th week: Only dinner was replaced.; Moderate Group: Replaced breakfast and dinner for 5 weeks and then only dinner during the next 7 weeks		12 weeks
Li et al[74]	United States	RCT	Clinical	46	SlimFast Food Company, Inc. West Palm Beach, FL 33401, United States	Replace 3 meals per day for first 5 days of the study. Replace 2 meals for three additional months. After three months, replace one to two meals per day with MR	/	12 months
Kempf et al[68]	Germany	Single-blind, active comparator, intervention study	Clinical	102	Almased-Vitalkost, Almased Wellness GmbH, Bienenbüttel, Germany	1st week: Replaced 3 main meals by 50 g PRMR = 1100 kcal/day; 2-4th week: 2 meals were replaced, and a low carb protein-rich lunch was allowed; 5-12th week: Only dinner was replaced	Weekly care calls (planned duration 20 minutes) from trained diabetes coaches. Received a weighing scale, and a step counter; TeLiPro group additionally received a blood glucose meter	12 weeks; 26 weeks and 56 weeks follow up without intervention
Shirai et al[91]	Japan	Randomized Trial	Clinical	119	Protein Sparing Formula Diet (Microdiet, Sunny Health Co. Ltd)	PMR; One pack of MR in the morning providing 240 kcal/meal; 2 conventional Japanese meal in noon and evening	/	24 weeks
Durrer et al[94]	Canada	RCT Protocol	Clinical	100	Commercial diet plan (Ideal Protein)	Commercial diet plan with pre-packaged foods used for two meals and one snack each day. The third meal prepared from lower-fat protein sources and low-carbohydrate vegetables.; Meal plan: 850-1100 kcal per day	/	12 weeks
Kempf et al[67]	Germany	RCT	Clinical	M: Moderate diet group 146; S: Stringent diet group 139	Almased-Vitalkost; Almased-Wellness-GmbH, Bienenbüttel, Germany	PMR; Contained 30.6 g carbohydrates and 1507 kJ (360 kcal) energy per 100 g powder	/	12 weeks of intervention, and 52 weeks of follow-up
Papakonstantinou et al[59]	Greece	Randomized, crossover Protocol	Clinical	17	Optifast by Novartis Hellas, S.A.C.I., Metamorfossi, Greece	PMR; Replaced breakfast and lunch and made up 26% of their energy intake	/	/
Low fat MR (n = 1)
Barbosa-Yañez et al[81]	Germany	randomized, parallel group, intervention study	Clinical	43	Flavoured meal replacement powder [MODIFAST® (OTC Siebenhandl GmbH) Ulm, Germany]	TDR; 1000-1200 kcal/day, and less than 30% of the total energy intake (E%) is fat; 200 g of raw or steamed vegetables	/	3 weeks of intensive low-fat diet, 49 weeks of eucaloric diet under DGE guidelines
MR + lifestyle intervention programme (n = 10)
Delahanty et al[121]	United States	Randomized, assessor-blinded, practice-based clinical trial	Clinical	69	Shakes, bars, and pre-packaged entrees	PMR; Use of meal replacements was recommended (but not supplied) for 1-2 meals per day starting in week 3 based on the Look AHEAD protocol. Meal replacement use was not formally tracked	Lifestyle intervention delivered by registered dietitian with 37 session identical contents in in-person and telephone arm.; Medical nutrition therapy participants were referred to a dietitian at their health center or preferred location as per usual care	12 months
Wycherley et al[95]	Australia	Randomized clinical trial	Community	37	KicStartä, Pharmacy Health Solutions, New SouthWales, Australia	PMR; High-protein, energy-restricted diet (5500 kJ/day)	A group of only diet. Another group of diet + exercise; Walking/jogging exercise programme comprising four to five exercise sessions per week	12 weeks
McDiarmid et al[60]	United Kingdom	RCT	Clinical	79	Optifast 820	TDR; 8 weeks of Optifast 820 kcal/3430 kJ formula diet, followed by 4 weeks of food reintroduction. Both groups were asked to complete 56 days during their active weight loss phase	After active weight loss phase, participants will be separated into two groups with CLED following a portion-controlled Mediterranean diet 7 days per week while ILED follows a MR diet for 1-2 days and portion-controlled Mediterranean diet for 5-6 days a week	12 months
Reynolds et al[122]	United States	RCT	Clinical	21	Pre-packaged entrees and low-calorie shakes (Health Management Resources, Boston, MA, United States)	PMR; Replace two meals with at least 1500 kcal per day	Placebo or Rosiglitazone 4 mg/day; Lifestyle programme with weekly behavioural education classes for 6 weeks then bi-weekly classes for remainder of the study	6 months
Hamdy and Carver[96]	United States	Intervention study	Clinical	85	BOOST Glucose Control (Nestlé HealthCare Nutrition, Inc., Minneapolis, MN, United States)	PMR; A meal plan with a 500-cal reduction rounded to the nearest 1200-, 1500-, or 1800-cal level	Weekly cognitive behavioural support; Weekly group education; Intensive and interactive diabetes medication adjustment; Individualized exercise plan	12 weeks
Pi-Sunyer et al[50]	United States	RCT	16 Clinical Centres	2496 (97.1%) ILI; 2463 (95.7%) DSE	4 meal replacements to choose: SlimFast (SlimFast Foods), Glucerna (Ross Laboratories), OPTIFAST (Novartis Nutrition) and HMR (HMR, Inc.)	First 3 weeks: Self-selected diet with energy goal for persons < 114 kg is 1200-1500 kcal/day and is 1500-1800 kcal/day for individuals ≥ 114 kg. First 6 months: Replace two meals and one snack a day with liquid shakes and meal bars (1200-1500 kcal/day); Months 7 onwards to year 4: Replace one meal and one snack per day; Calorie targets personalized based on participants weight loss goals	1 hour diabetes education class on first visit + Three group educational/social support sessions each year for 4 years; Physical activity + Behavioural techniques	Intensive intervention for first 4 years, with an average of 10.25 years follow up
Lean et al[18]	United Kingdom	RCT	Clinical	149	Counterweight-Plus MR	TDR phase using a low energy formula diet (825-853 kcal/day)	Counterweight-Plus weight management programme	Total diet replacement of 3-5 months with stepped food reintroduction of 2-8 weeks and long-term weight maintenance program until month 12
Sattar et al[78]	United Kingdom	RCT	Clinical	25	TDR with Low energy liquid formula diet (Counterweight Pro 800)	Initial Total Diet Replacement phase (3-5 months); A commercial micronutrient-replete 825-853 kcal/day LELD is provided (Counterweight Pro 800) to replace normal foods	Counterweight-Plus’ weight management programme; Structured food reintroduction (6-8 weeks)	3 months minimum
Marples et al[79]	United Kingdom	Intervention study/service evaluation	Clinical	37	Phased LED TDR and PMR with Counterweight TDR products	TDR phase: 825-853 kcal/day; Food reintroduction phase: Gradual reduction in the formula product and the incorporation of nutritionally dense and energy-restricted meals (360-400 cal per meal). Weight Loss Maintenance phase	Behhaviour change techniques	TDR phase: 12 weeks; Food reintroduction phase: 9 weeks; Weight Loss Maintenance phase: 31 weeks
Dasgupta et al[62]	United Kingdom and Canada	RCT protocol	Clinical	50	Phased TDR and PMR with Optifast products (Nestlé)	First 2 weeks: Optifast products (Nestlé), totalling 800-900 kcal/day (30% protein, 50% carbohydrate and 20% fat).; Week 3-12: PMR with 800-900 kcal daily on non-exercise days and an additional 150-200 kcal from meal replacement products on exercise days. Week 12-24: Maintainence phase, individualized meal plan	Exercise training	24 weeks: 12 weeks MR and 12 week maintainence

RCT: Randomized controlled trial; MR: Meal replacement; PMR: Partial meal replacement; TDR: Total diet replacement; LCD: Low calorie diet; VLCD: Very low calorie diet; LELD: Low energy liquid diet; TEI: Total energy intake; VLED: Weight Plan products; DSNF: Diabetes specific nutrition formula; BMI: Body mass index.

Table 3 Outcome of meal replacement on hemoglobin A1c, glucose, weight, other health status and adverse effects.

Ref.	Year	HbA1c	Glucose	Weight (kg)	Lipid profile	Other health status	Adverse effects
Low calorie/energy MR (n = 32)
Rothberg et al[75]	2014	1R	/	1R	/	/	Not reported
Tatti et al[41]	2010	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; HDL - 2I	SBP - 1R; DBP - 1R	Not reported
Steven et al[51]	2016	1R	1R	1R	1R	Plasma insulin levels - 1R	Not reported
Shantha et al[101]	2012	1R	/	1R	/	/	Not reported
Astbury et al[35]	2018	1R	1R	1R	NC	HOMA-IR - 2I	Constipation (1 in 7), fatigue (1 in 12), Headache (1 in 17), dizziness (1 in 22)
Baker et al[52]	2011	/	/	1R	/	Plasma insulin levels - 1R	Not reported
Bhatt et al[82]	2017	1R	1R	1R	Triglycerides - 1R; HDL - NC; LDL - NC	/	Not reported
Berk et al[42]	2016	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; HDL - 2I; LDL - 1R; Non-HDL Cho - 1R	/	Not reported
Shiau et al[54]	2017	1R	/	1R	/	/	Not reported
Cinkajzlová et al[102]	2017	/	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; HDL - 2I; LDL - 1R	/	Not reported
Taheri et al[40]	2019	1R	/	1R	Total cholesterol - 2I; Triglycerides - 1R; HDL - 2I; LDL - 2I	Diabetes remission% - 1R; Quality of life - 2I	Dizziness, constipation and other gastrointestinal; symptoms, hair loss, and fatigue
Harder et al[83]	2003	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; LDL - 1R	/	Not reported
Friedman et al[84]	2013	1R	1R	1R	/	Serum creatinine, cystatin C and estimated glomerular filtration rate- 1R; Albuminuria - 1R	Elevations in BUN and serum creatinine early in the diet, resolved after reducing doses of antihypertensive medications
Lean and Leslie[77]	2017	1R	/	1R	/	/	Not reported
Leader et al[55]	2012	1R	/	1R	/	/	Not reported
Overl et al[104]	2017	1R	/	1R	/	/	Not reported
Gulsin et al[69]	2020	1R	/	1R	/	Blood pressure - 1R	Not reported
Farrer and Golley[36]	2013	1R	/	1R	Cholesterol - NC	/	Not reported
Sumithran and Proietto[56]	2008	1R	1R	1R	/	/	Not reported
Rolland et al[105]	2013	/	/	1R	/	/	Not reported
Dhindsa et al[71]	2003	1R	/	1R	1R	BP - 1R	Not reported
Khoo et al[85]	2011	/	1R	1R	LDL - 1R	Quantitative Insulin Sensitivity check - 2I	Not reported
Moriconi et al[97]	2021	1R	/	1R	Total cholesterol - 1R	SBP - 1R	Not reported
Tang and Lin[86]	2020	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; HDL - 2I; LDL - 1R	/	Not reported
Maher et al[106]	2019	1R	/	1R	/	/	Not reported
Nori Janosz et al[34]	2008	1R	NC	1R	/	/	Not reported
Storck et al[57]	2021	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R	WC - 1R; Liver profile - 1R; Insulin and HOMAIR - 2I	Constipation (n = 5)
Schwasinger-Schmidt et al[107]	2020	1R	1R	1R	/	/	Not reported
Steven and Taylor[58]	2015	1R	1R	1R	1R	/	Not reported
Redmon et al[72]	2003	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; LDL - 1R	/	Dry mouth; Constipation; Mild hypoglycemia
Lips et al[87]	2014	/	1R	1R	/	HOMA-IR - 1R	Not reported
Abi-Chahine et al[108]	2021	1R	/	1R	/	Quality of life - 2I	Not reported
Rafey et al[113]	2022	1R	/	/	/	Leptin - 1R; Adiponectin - 2I	Not reported
Hocking et al[61]	2023	1R	/	1R	/	/	Two serious adverse events - hypotension
Anyiam et al[99]	2023	/	/	R	/	/	/
De Freitas et al[115]	2023	R	R	R	Total cholesterol - R; Triglycerides - R; HDL - I; LDL - R	HOMA-IR - R	/
Khoo et al[116]	2023	1R	/	1R	/	/	/
Low Glycemic Index MR (n = 5)
Stenvers et al[28]	2014	NC	1R	NC	NC	/	Altered defecation pattern and/or flatulence - n = 8; Nausea - n = 1; Mild attack of gout - n = 1
Foster et al[88]	2013	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; HDL - 2I; LDL - 1R	BP - 1R	No related adverse effects
Boonyavarakul et al[39]	2018	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 2I; LDL - 1R	/	Not reported
Li et al[33]	2014	1R	NC	1R	/	/	Not reported
Eliana and Pranoto[117]	2018	/	1R	/	/	/	Vomiting - n = 1; Soft stools - n = 1
Santen et al[89]	2023	1R	/	1R	Total cholesterol - R	/	/
Diabetes specific formulas (n = 13)
Belcaro et al[32]	2009	1R	1R	1R	/	/	No adverse effects
Fonda et al[43]	2010	/	1R	/	/	/	Not reported
Garvey et al[119]	2006	1R	1R	1R	HDL-C - 2I	Insulin sensitivity - 2I; SBP and DBP - 1R; Quality of life - 2I	Not reported
Sun et al[37]	2008	1R	1R	1R	NC	/	Not reported
Peng et al[44]	2019	1R	1R	1R	Triglycerides - 1R	SBP - 2I; HOMA-IR - 2I	Not reported
Chee et al[45]	2017	1R	1R	1R	HDL - 2I; LDL - 1R	SBP - 1R	Not reported
Lansink et al[31]	2011	/	NC	1R	/	/	Low incidence and mild intensity of reported abdominal pain
Mottalib et al[30]	2018	1R	NC	1R	Total cholesterol - NC; HDL - 2I; LDL - NC	/	Not reported
Otto et al[48]	2009	1R	/	1R	/		Not reported
Yip et al[73]	2001	1R	1R	1R	Total cholesterol - 1R; LDL - 1R	Insulin levels - 1R	Not reported
Mottalib et al[38]	2016	/	1R	/	NC	/	Not reported
Cheskin et al[80]	2008	1R	1R	1R	HDL: 34 weeks - 2I; 86 weeks - 2I	SBP and DBP - 1R	Not reported
Mustad et al[49]	2020	/	1R	/	/	/	Not reported
Dharmalingam et al[93]	2022	1R	1R	1R	Total cholesterol - R; Triglycerides - R; HDL - I; LDL - I	/	No serious adverse events; Six mild adverse effects: Loss of appetite, stomach bloating, peripheral leg edema, burning micturition, and urinary retention
Zagury et al[100]	2022	/	1R	/	/	/	No serious adverse events. 4 participants (13%) had mild diarrhea and 3 participants (10%) had mild nausea
Protein rich MR (n = 10)
Keogh and Clifton[90]	2012	1R	1R	1R	Total cholesterol - 1R; Triglycerides - 1R; LDL - 1R	SBP and DBP - 1R	Not reported
Navas-Carretero et al[29]	2011	/	NC	1R	NC	/	Not reported
Kempf et al[64]	2014	1R	1R	1R	Triglycerides - 1R; HDL - 2I	/	Not reported
Kempf et al[65]	2014	/	/	1R	/	SBP and DBP - 1R	Not reported
Kempf et al[120]	2015	1R	/	1R	/	/	Not reported
Martin et al[66]	2014	1R	/	1R	/	/	Not reported
Li et al[74]	2005	1R	1R	1R	/	High-sensitivity C-reactive protein - 1R	Not reported
Kempf et al[68]	2017	1R	1R	1R	/	SBP - 1R; Quality of life and eating behaviour - 2I	Not reported
Shirai et al[91]	2013	1R	1R	1R	HDL - 2I	Insulin and HOMAIR - 1R; Leptin - 1R; Adiponectin - 2I; Lipoprotein lipase mass - 2I	Not reported
Kempf et al[67]	2018	1R	1R	1R	/	/	Not reported
Low fat MR (n = 1)
Barbosa-Yañez et al[81]	2018	1R	/	1R	1R	/	Not reported
MR + lifestyle intervention programme (n = 9)
Delahanty et al[121]	2020	1R	/	1R	/	/	Not reported
Wycherley et al[95]	2008	/	1R	1R	/	/	Not reported
Reynolds et al[122]	2002	1R	/	1R	Total cholesterol - 1R; LDL - 1R	WC- 1R; BP - 1R	Not reported
Hamdy and Carver[96]	2008	1R	/	1R	1R	/	Not reported
Pi-Sunyer et al[50]	2009	1R	1R	1R	Triglycerides - 1R; HDL - 2I	WC - 1R	Not reported
Lean et al[18]	2018	1R	/	1R	/	Quality of life - 2I	65% reported constipation, 57% reported sensitivity to cold and 53% reported headache
Sattar et al[78]	2023	R	R	1R	Total cholesterol - R; HDL - R	WC - R	/
McDiarmid et al[142]	2021	R	/	1R	/	/	/
Marples et al[79]	2022	1R	/	1R	Total cholesterol - R; Triglycerides - 1R; HDL - I; LDL - R	/	No serious adverse events were reported.; Mild side-effects: Constipation, diarrhoea, nausea, fatigue and feeling cold

¹Significant reduction.

²Significant increment.

I: Non-significant increment; R: Non-significant reduction; NC: No changes; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; HOMA-IR: Homeostatic model assessment of insulin resistance; WC: Waist Circumference; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HbA1c: Hemoglobin A1c.

Low calorie/energy meal replacement

A total of 46 studies reported low calorie meal replacements interventions with intervention durations lasting from three weeks to 15 months[34-36,40-42,51-58,61,69-72,75-77,82-87,97,99,101-116]. Among the studies, twenty two studies reported utilizing total diet replacement with meal replacements, with daily calorie allowances ranging from 456 kcal to 1200 kcal per day[35,51-54,58,69,70,75,77,82,83,87,99,104-108,112,114,115]. Eleven studies reported the usage of partial meal replacement, replacing 206 kcal to 450 kcal per serving with a target of 800 kcal to 1300 kcal per day[34,41,42,55,71,72,84-86,103,116]. Ten studies utilized a phased low-calorie meal replacement intervention which involved full meal replacement at the initial stage, followed by a partial meal replacement plan with food reintroduction[36,40,56,57,61,76,97,110,111,113]. One study reported usage of an individualized meal replacement plan aimed at achieving 1000 kcal deficit per day[101].

Among the low-calorie meal replacement interventions, 32 studies reported reduction in HbA1c levels which corresponded to reduction in fasting plasma glucose levels reported in 17 studies[35,41,42,51,56-58,72,82-87,102,107,115] and improvements in plasma insulin level in four studies[51,52,87,115]. Only one study reported no changes in fasting plasma glucose level after a short-term meal replacement intervention of 4 weeks[34].

Thirty-six studies reported significant weight loss after low-calorie meal replacement interventions. This also corelated well with the improvement of lipid profiles as reported in 15 studies[40-42,51,57,58,71,72,82,83,85,86,97,102,115]. Even in a short-term low-calorie meal replacement as brief as 3 weeks, the participants have reduced their mean body weight from 112 kg to 105.3 kg[87].

Low GI meal replacement

Six studies were reported with an intervention using low GI meal replacements[28,33,39,88,89,117]. The low GI meal replacement was categorized according to the specification by the authors and had the GI of the meal replacement products stated. The utilized meal replacement products had GI ranging from 19 to 35. Among the six studies, two study utilized full meal replacements[89,117] while four studies utilized partial meal replacement[28,33,39,88] with an intervention period of 8 days to 6 months.

Among five studies which reported HbA1c outcomes, three studies had improved HbA1c levels from 0.2% to 1.83%[33,39,88,89] while one had no changes in the HbA1c levels after low GI meal replacement intervention[28]. Four studies reported a reduction in glucose level after meal replacement consumption[28,39,88,117]. Only three studies reported a significant weight loss after the intervention in which the lipid profile was also improved in the same study[39,88,89].

Diabetes specific formulas

The studies included in this category were those in which the meal replacements were specified by the authors as diabetes-specific formulas. All the studies utilized the diabetes-specific formulas as partial meal replacements, with 12 studies providing a single meal replacement per day[37,38,43,44,47,49,80,92,93,98,100,118] and another eight providing two or more replacements per day[30-32,45,46,48,73,119]. Intervention period for these studies was 1 week to 34 weeks.

Of the 10 studies that reported HbA1c outcomes, all of them reported reduction in HbA1c levels which correlated with nine studies that reported improvement in glucose levels[30,32,37,44,45,73,80,93,119]. All the studies that reported body weight demonstrated improvements in body weight[30-32,37,44,45,48,73,80,93,119]. Six out of nine studies which reported lipid profiles showed positive improvements in lipid profile levels[30,44,45,73,80,119].

Protein-rich meal replacements

Thirteen studies reported utilizing protein-rich meal replacements in their intervention with duration of intervention ranging from 4 to 24 weeks[29,59,63-68,74,90,91,94,120]. Nine studies utilized the meal replacement as a structured meal replacement plan[29,63-66,68,74,90,94] while four used them as partial meal replacements[59,67,91,120].

Eight studies which reported HbA1c outcome showed improvement in HbA1c levels[64,66-68,74,91,120] while six out of seven studies that reported glucose levels showed positive improvements[64,67,68,74,90,91]. All studies have shown a reduction in body weight after the protein-rich meal replacement intervention[29,64-68,74,90,91,120]. Lipid profile improved in three of the included studies[64,90,91].

Low-fat meal replacements

There was only one study under the category of low-fat meal replacements which involved utilizing a 3 weeks’ intensive total diet replacement with a target of 1200 kcal per day and less than 30% of total energy intake was fat[81]. HbA1c was reduced by 0.1% but not significant while body weight and lipid profile improved significantly.

Combined meal replacements with lifestyle intervention programs

Ten of the reported studies were not exclusively nutritional based. Instead, the intervention focused on a combination of meal replacements and lifestyle intervention programs, from exercise sessions to intensive lifestyle interventions (ILI) consisting of behavioral classes, diet modifications and supervised physical activities as described in the Look AHEAD and DIRECT studies[18,50,60,62,78,79,95,96,121,122]. The ILIs were delivered by trained physicians, nurses, and dietitians. Most of the studies in this category had a longer duration of intervention with at least 12 weeks to 4 years, and follow-up period of up to 10 years.

Overall, the reported HbA1c outcome decreased significantly compared to baseline ranging from -0.64% to -3.6%. All the studies also had reported significant reduction in body weight, with four studies demonstrating improved lipid profile levels[50,79,96,122].

Adverse events

Only 13 studies reported the occurrence of mild adverse effects throughout the intervention[18,28,31,35,40,57,61,72,79,84,93,100,117]. However, most of the incidents were mild events, such as constipation and other altered defecation patterns, sensitivity to cold, headache, abdominal pain, nausea, stomach bloating, peripheral leg edema, dizziness and fatigue. Among them, constipation was the most reported adverse effect[18,35,40,57,72,100].

DISCUSSION

This scoping review compiled existing literature to explore the use of meal replacements in the dietary management of patients with T2D. It examined the types of meal replacements available for T2D and evaluated their impact on glucose/HbA1C, weight/BMI, and other health outcomes. Additionally, the review identified the potential adverse effects associated with meal replacements.

According to the classification of studies by continent or country, the utilization of meal replacements was predominantly studied in higher income settings, with 47 studies conducted in United states and Europe, including 12 studies from the United Kingdom. However, as shown in a study by Kaiser et al[123], it was estimated that in 2018, the prevalence of T2D to be similar across high- and low-income countries. The prevalence of diabetes has risen more rapidly in low- and middle-income countries compared to high-income nations[124]. While lifestyle interventions have been found to have an ethnic nonspecific benefits, their implementation in low- and middle-income countries remains underrepresented in the literature[125]. From our review, there is a lack of meal replacement intervention trials from Southeast Asia, South Asia, and Africa.

Among the few studies included in our review that were conducted in low- and middle-income countries, all but one demonstrated significant improvements in HbA1c, blood glucose, and weight or BMI. These suggest clinical effectiveness across different populations. However, the generalizability of findings from high-income settings to low- and middle-income countries may be limited. Differences in food preference and availability, dietary practices, and nutrition status, can influence the safety, acceptability, and efficacy of meal replacement interventions.

In addition, barriers, such as limited access to dietitians and lack of structured diabetes care, can further challenge the real-world implementation of meal replacement in the region. Many commercially available meal replacements are costly or unavailable in these settings. Despite being crucial for public health adoption, limited studies have evaluated their cost-effectiveness in low- and middle-income countries[126].

Through this review, we found that over 60% of the studies were performed together with diet education commonly administered via a dietitian or physician. These studies often involved weekly follow-ups and visits to encourage consistent participation in the intervention. This observation reflected the real-world feasibility in an outpatient clinical setting. Individuals that participated in a meal replacement program have cited that health coaching support facilitated them in the weight loss maintenance phase[127]. A review by Maula et al[128] highlighted that meal replacements, when combined with education, were among the most effective strategies for achieving significant reductions in weight and BMI for individuals with T2D. Wan Rohimi and Mohd Tahir[129] also found that most education approaches were cost-effective and effective in improving self-efficacy in managing T2D.

While detailed comparisons between professional roles and outcomes were limited, the consistent involvement of dietitians, either independently or alongside physicians, was common among studies that demonstrated positive metabolic outcomes. The variation in counseling duration and frequency suggests that regular sessions as brief as 15 minutes may be effective, highlighting the importance of accessible, multidisciplinary support. These findings underscore the potential benefit of multidisciplinary approaches into future interventions for people with T2D.

The increasing use of GLP-1 receptor agonists, such as semaglutide and liraglutide, has significantly advanced pharmacologic options for glycemic management and weight reduction in T2D. However, their real-world application is often constrained by high costs, limited accessibility, and gastrointestinal side effects, contributing to discontinuation in a considerable proportion of users[130,131]. In contrast, meal replacements offer a structured, non-pharmacologic alternative with demonstrated benefits on weight and glycemic outcomes. Economic evaluations highlight the cost-effectiveness of meal replacements in some of the past studies. For example, the OPTI program reported substantial cost savings of $24487 per person compared to no intervention and $18034 compared to liraglutide 3 mg, while also generating 1.133 and 0.734 additional quality-adjusted life years (QALYs), respectively[132]. Similarly, a diabetes specific meal replacement-based intervention demonstrated an incremental cost-effectiveness ratio of $47917 per QALY gained, positioning it well within commonly accepted cost-effectiveness thresholds[133]. Given these factors, meal replacements may serve as a viable alternative for individuals unable to sustain long-term GLP-1 therapy, warranting further integration into multidisciplinary care models.

However, despite favorable economic evaluations, the cost of meal replacements may remain a barrier for individuals with limited financial resources, highlighting the need for studies to explore more affordable alternatives and the integration of meal replacements into subsidized healthcare or public nutrition programs.

The present findings demonstrate that 95% of the studies have reported effective weight reduction even after 3 weeks of intervention. One of the largest diabetes weight management interventions, the Look AHEAD study, has reported a significant weight loss of approximately 8.6% as compared to 0.7% in control group with similar calorie intake per day[50]. Another study by Astbury et al[134] compared two studies with similar behavioral program and found that incorporating meal replacement enhanced their effectiveness among participants with overweight, with 2.22 kg greater weight loss at 1 year. Similarly, the OPTIWIN study on participants with obesity has found that total meal replacement has generated more effective and sustainable weight loss of 10.5% ± 0.6% compared to 5.5% ± 0.6% for participants on food-based diet plans at 52 weeks[135]. The weight reduction in meal replacement group might be caused by the reduced energy intake. This is common in our findings in which participants consuming low-calorie meal replacements experienced weight reduction. A systematic review on nine VLEDs studies has also shown that VLEDs are effective for substantial weight loss among participants with T2D[136].

The amount of weight loss might also result in significant improvement in diabetes control with reductions in HbA1c and glucose levels. American Heart Association/American College of Cardiology also reported that weight loss of more than 5% can lower HbA1c level by 0.6%-1.0%. A review by Churuangsuk et al[137] found that the main contributor to HbA1c reduction and remission was weight loss. From our findings, 98% of the studies in this review reported a reduction in HbA1c levels.

Among the meal replacements used, all 10 studies that utilized diabetes-specific formulas solely as intervention have shown significant improvements in HbA1c levels[30,32,37,44,45,48,73,80,93,119]. This is probably due to the presence of high fat, high fiber, and low carbohydrate content normally present in the diabetes-specific formulas, leading to lower GI as well as better glycemic management as compared to other formula diets. The Look AHEAD study has demonstrated a change of -0.64% in HbA1c in the ILI utilizing a diabetes-specific meal replacement vs -0.14% in the standard diet group from a baseline of approximately 7.3% in both groups (P < 0.001) at 1 year[50]. This was also followed by the subsequent reduction in glucose-lowering medication used in the intensive lifestyle intervention group.

The reduced energy intake from meal replacement interventions, along with their low GI nature, may contribute to improved glycemic management by attenuating postprandial glucose spikes, decreasing insulin secretion, and enhancing insulin sensitivity. Meal replacement interventions have also been associated with increased adiponectin levels, which promote glucose uptake and fatty acid oxidation[138,139]. Improved leptin sensitivity, linked with meal replacement usage, may aid in appetite regulation[113]. These hormonal changes may reduce insulin resistance and contribute to sustained improvements in glycemic and weight outcomes in individuals with T2D.

Reductions in biochemical values of lipid profile (cholesterol, triglycerides, LDL and HDL) were also observed. For example, in an RCT with low-fat meal replacement, 3 weeks of total diet replacement was able to improve the lipid profile significantly[81]. In the other intervention utilizing diabetes-specific meal replacements, six out of nine studies also reported a reduction in lipid profile. Participants with obesity undergoing partial meal replacement intervention also reported that the levels of total cholesterol, triglycerides and LDL significantly decreased with a significant increase in HDL levels after 8 weeks of intervention.

Only 13 studies reported occurrence of adverse events[18,28,31,35,40,57,61,72,79,84,93,100,117]. The most reported adverse effect was constipation which might be due to the inadequate fiber consumption during meal replacement interventions[18,35,40,57,72,79]. Another review of meal replacement utilization on weight loss programs reported that the overall nutritional quality of the diet may be further improved[134].

Strengths, limitations and recommendations

The findings from the review can help provide new evidence to supplement the existing clinical guidelines regarding utilization of meal replacement for management of T2D as well as obesity. This scoping review has some strengths that provide validity and reliability as a literary map or overview for rapid analysis in the field. Sixty-six articles in this review are protocols or reports from randomized controlled trial, improving the credibility of the reported outcomes. The total sample size included in this review was 8543 participants with T2D. This review has also included studies over 12 months of follow up as T2D is a progressive chronic disease. Lifestyle interventions of < 3 months often report beneficial effects, but it is also important to understand the effects of the longer-term interventions as well as their sustainability.

There are also some limitations in this review that should be noted. Despite employing a broad search strategy without language restrictions, most of the included studies involved European participants, which may limit the generalizability of the findings to other ethnic groups or communities. Secondary analyses of several large studies have been excluded from the review because they could not satisfy the study inclusion criteria.

Another limitation on the current body of evidence is the lack of homogeneity across studies. The included studies varied significantly in design, ranging from randomized controlled trials to observational studies, which differed in methodological strength and possible bias. Intervention durations were also inconsistent, with some lasting only a few weeks while others extending up to 2 years, making direct comparisons difficult. Furthermore, the definition and reporting of adverse effects lacked standardization, which challenges the ability to draw firm conclusions about safety profiles.

There were also considerable variations in the composition of meal replacement used, including differences in macronutrient content, GI, and presence of functional ingredients. These factors complicate cross-study comparisons. Furthermore, retention rates and dropout data were inconsistently reported, making it difficult to evaluate real-world feasibility. This scoping review approach allowed for the inclusion of a broader range of studies, regardless of study heterogeneity. However, more definitive conclusions on effectiveness and implementations should be further evaluated through meta-analyses.

After evaluating the studies included in this review, there are several recommendations that can be suggested for future research. First, there is a lack of meal replacement studies in Africa and Asia, apart from China. The population in Africa and South Asia is under-represented in the study pool. Attention needs to be given to these regions especially in the Southeast Asia as more than half (56%) of all people with diabetes were found to be residing in the Southeast Asian or Western Pacific regions[140]. Genetic variations and ethnic differences should be considered when incorporating nutritional strategies in lifestyle intervention programs. There is also a lack of study on assessing the underlying mechanisms of meal replacement on T2D. More studies on the underlying changes of hormones related to glycemic management and weight control such as adiponectin and leptin should be conducted. Some other meaningful and significant outcomes should also be assessed in future studies, such as quality of life and cost effectiveness to further justify the utilization of meal replacement in clinical practice settings.

Future meal replacement studies should also focus on methods to measure retention rate and nutrient intake more accurately. Although meal replacements with standard formulas like VLEDs have been used extensively for management in T2D and yield positive results in weight reduction and glycemic management, there are still adverse effects, especially constipation as shown in some of the studies included in our review. Diabetes-specific formulas are developed to provide a more complete nutrient package for patients with T2D, but it is not extensively studied worldwide and sometimes too costly for populations in low-income countries. Hence, efforts to develop an ideal nutritional formula for patients with different backgrounds and regions should be continued.

CONCLUSION

This review has enabled us to map and summarize the types and dosage of meal replacements utilized, along with findings from existing studies to highlight the limitations and propose recommendations for future research in nutritional interventions for diabetes. In conclusion, the review provides evidence that meal replacements, particularly when combined with lifestyle intervention programs and education or counseling, serve as an effective and safe strategy for glycemic management and promote weight reduction in patients with T2D. Therefore, incorporating meal replacements as part of lifestyle intervention programs is a viable recommendation for managing T2D.

ACKNOWLEDGEMENTS

The authors would like to thank the National University of Malaysia (UKM) for the provision of resources towards this review and the Centre for Healthy Ageing and Wellness (H-CARE) UKM for training and technical support.