Randomized, controlled trials (RCTs) comparing the effectiveness of metabolic bariatric surgery (MBS) in addition to one or more treatment interventions for obesity (i.e., lifestyle structured interventions-LSI, medical therapy-MT, obesity management medication-OMM or endobariatric procedures-EP) are lacking. This study aims to assess the effectiveness of multiple simultaneous (before or immediately after MBS) interventions for treating obesity.

We performed a meta-analysis including all RCTs enrolling patients undergoing different MBS procedures add-on to other anti-obesity strategies (LSI, MT, OMM or ES) versus MBS alone, with a duration of at least 6 months. The primary outcome was BMI at the end-point; secondary end-points included percentage total and excess weight loss (%TWL%, and EBWL%), total weight loss (TWL), fasting plasma glucose (FPG), HbA1c, surgical and non-surgical severe adverse events (SAE), mortality, remission of type 2 diabetes, hypertension, dyslipidemia and health-related quality of life (HR-QoL).

A total of 25 RCTs were retrieved. The addition of either OMM (i.e., liraglutide) or EP (i.e., intragastric balloon-IB, endosleeve-ES) to MBS was associated with a significantly lower BMI at the end-point (p = 0.040). The addition of liraglutide only to MBS was associated with a greater %EWL%, but not %TWL and TBWL (p = 0.008). Three trials evaluated end-point HbA1c, showing a significant reduction in favour of liraglutide as an add-on therapy to MBS (p = 0.007). There was no mortality.

MBS combined with non-surgical approaches appears more effective than MBS alone in reducing BMI. Further RCTs on combined therapies to MBS for severe obesity are needed to enhance the tailoring of treatment for severe obesity.

Mental illnesses and psychotropic drug use are associated with an increased risk of weight gain and metabolic disorders. Growing evidence suggests that agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) might be safe and effective weight loss medications. However, the current evidence for the use of GLP-1RAs in individuals with obesity and mental illness is limited.

Evaluation of the safety and the impact of GLP-1RAs on mental health and psychotropics-induced metabolic disorders such as obesity and type 2 diabetes (T2D).

A literature search from January 1st, 2010 to August 31st, 2024 was conducted using PubMed and Cochrane Library online databases. Studies comprising adults with obesity or/and T2D and mental illness were included. Studies that examined individuals with obesity or/and T2D without mental illness and completed psychiatric questionnaires before and after GLP-1RAs treatment were also included.

From the 36 included studies 18 examined the weight-reducing effect of GLP-1RAs in patients with mental disorders and the other studies examined patients without mental illness. GLP-1RAs lead to a significant weight loss and improvement of glycemic control in patients with mental illness on psychotropics. They showed a beneficial effect on mental health in patients with and without mental disorders and were not associated with a worsening of mental state, suicidality, new-onset mental illness, or increased psychiatric admissions.

GLP-1RAs are safe and effective weight loss treatments for individuals with obesity and mental illness exerting a positive effect on mental state and quality of life. There is a need for RCTs with larger sample sizes, a longer treatment duration and longer follow-up periods to evaluate the long-term effect of GLP-1RAs. It would be of great interest to conduct studies investigating the use of GLP-1RAs with the purpose to treat mental illness in order to directly assess their use in improving mental health.

Obese patients experience more complications after autologous breast reconstruction. This study evaluates how bariatric surgery modulates risk of complications in the setting of microvascular breast reconstruction.

Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program databases were queried for patients with body mass index (BMI) greater than or equal to 35 kg/m 2 undergoing bariatric surgery from 2017 to 2022. Outcomes included BMI and obesity-related comorbidities before and 1 year after bariatric surgery. Paired Breast Reconstruction Risk Assessment scores were analyzed to evaluate risk modulation before and after bariatric surgery in the setting of microvascular breast reconstruction.

A total of 1026 patients were included with an average age of 47 and BMI of 44.7 kg/m 2 . Comorbidities included hypertension ( n = 601 [59%]), type 2 diabetes ( n = 291 [28%]), and cardiovascular disease ( n = 10 [1%]). One-year outcomes after bariatric surgery included an average BMI of 32.7 kg/m 2 , with remission of type 2 diabetes in 29% of patients. Paired Breast Reconstruction Risk Assessment analysis for microvascular breast reconstruction before and after bariatric surgery showed reduction in 30-day surgical complications (40.4% versus 24.8%; P < 0.0001), with an absolute risk reduction of 15%, a relative risk reduction of 36%, and a number needed to treat of 7. Each 1-kg/m 2 reduction in preoperative BMI was associated with a 3.4% reduction in surgical complications ( P < 0.0001).

There is potential efficacy for metabolic bridge therapy in reducing complications for obese patients undergoing microvascular breast reconstruction.

Risk, IV.

Obesity and thyroid dysfunction are among the most significant challenges in endocrinology, frequently overlapping to create complexities in weight management. Even after achieving euthyroidism, weight variations persist, significantly affecting patients' quality of life. This review explores the mechanisms linking hypothyroidism and hyperthyroidism to weight fluctuations, emphasizing their impact on basal metabolic rate, appetite regulation, glucose and lipid metabolism, and thermogenesis.

We conducted a comprehensive review using PubMed and Google Scholar, applying the search criteria: (obesity OR overweight) AND (Hashimoto's thyroiditis OR hyperthyroidism OR hypothyroidism OR Thyroid Cancer). From this search, we reviewed 500 publications and finally included 71 publications, focusing on broad clinical questions regarding the role of thyroid hormones in weight regulation and metabolism, the impact of thyroid disorders and their treatments on obesity, and approaches for managing obesity in the context of thyroid dysfunction.

In hypothyroidism, the impact of levothyroxine therapy on weight changes is discussed, along with the potential role of T3 supplementation. For hyperthyroid patients, the effects of antithyroid medications, radioactive iodine therapy, and thyroidectomy on weight regulation are explored. Pharmacological and nonpharmacological strategies for managing obesity in thyroid disorders are reviewed. Lifestyle interventions and pharmacotherapies are evaluated for their efficacy and potential effects on thyroid function. Lastly, the implications of bariatric surgery are explored, including its effects on thyroid function, medication absorption, and postsurgical management of thyroid disorders.

This review underscores the importance of an integrated, multidisciplinary approach to managing obesity in the context of thyroid dysfunction to optimize patient outcomes.

Bariatric surgery has long been the most effective intervention for obesity, providing significant and durable weight loss, with procedures like sleeve gastrectomy and gastric bypass achieving 10-year total weight loss (TWL) rates of 23.4% and 26.9%, respectively. More complex procedures, such as duodenal switch, result in even greater TWL. Recently, glucagon-like peptide-1 receptor agonists (GLP-1 RA) have emerged as a promising pharmacological alternative, demonstrating up to 25.3% TWL with tirzepatide. However, GLP-1 RA efficacy remains inferior to bariatric surgery, with high discontinuation rates due to adverse effects, cost, and limited insurance coverage. While surgery offers superior long-term outcomes and cost-effectiveness, it is underutilized, with less than 1% of eligible patients undergoing surgical intervention annually. GLP-1 RA can expand access to obesity treatment, particularly for patients hesitant or ineligible for surgery, and may serve as a bridge to surgery or an adjunct for postoperative weight regain. Despite their benefits, GLP-1 RAs require sustained adherence, and weight regain is common upon discontinuation. A multidisciplinary approach integrating surgical, pharmacological, and lifestyle interventions is essential for optimizing obesity management. Future research should focus on long-term GLP-1 RA efficacy, combination therapy strategies, and improving access to both surgical and medical obesity treatments.

Obesity can impair cardiometabolism, but low-carbohydrate diets (LCDs) may be beneficial for mitigating risk. We aimed to investigate the effects of LCDs versus low-fat diets (LFDs), under hypocaloric conditions, on flow-mediated dilation (FMD) in individuals with overweight/obesity. Secondarily, we assessed other cardiovascular markers (systolic blood pressure, diastolic blood pressure, C-reactive protein [CRP], high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides [TG], total cholesterol [TC]), and anthropometric and body composition measurements. PubMed, Scopus, and Web of Science were searched through May 2023 for studies involving hypocaloric LCDs versus LFDs on FMD. Meta-analyses were conducted for LCDs vs. LFDs to calculate weighted mean differences (WMD), including 10 studies reporting FMD (n = 475). Overall, hypocaloric LCDs resulted in a non-significant decrease in FMD compared with hypocaloric LFDs [WMD = -1.04% (95% CI -2.28 to 0.20), p = 0.10], while very-low-carbohydrate diets (VLCDs) significantly reduced FMD when compared with LFDs [WMD = -2.12% (95% CI: -3.35 to -0.9) p = 0.001]. LCDs did not change anthropometric and body composition measurements, nor CRP, blood pressure, HDL, or TC when compared with LFDs. However, LCDs significantly decreased TG [WMD = -19.94 mg/dL (95% CI -31.83 to -8.06), p = 0.001] and increased LDL [WMD = 20.00 mg/dL (95% CI 14.09 to 25.90), p = 0.001] when compared with LFDs. In conclusion, LCDs did not exert superior effects on cardiovascular markers or body composition when compared with LFDs in individuals with overweight or obesity, but LCDs reduced TG and increased LDL levels more than LFDs. Yet, vascular function (FMD) was reduced primarily for VLCDs.

Although the cardioprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well documented in patients with diabetes mellitus, their impact on cardiovascular outcomes in patients with obesity without diabetes remains under debate. Therefore, we conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of GLP-1 RAs on cardiovascular outcomes in patients with obesity without diabetes.

We systematically searched PubMed, Web of Science, SCOPUS, and Cochrane databases through December 26, 2023. We pooled dichotomous data using risk ratios (RRs) and continuous data using mean differences with 95% confidence intervals (CIs). We evaluated the quality of each study using the Cochrane RoB2 method, and the study protocol was registered on PROSPERO ID: CRD42024498538.

We included 19 RCTs with a total of 32,884 patients. Of these, 15 had a low overall risk of bias, two raised concerns, and two had a high risk of bias. There was no difference between GLP-1 RAs and placebo regarding cardiovascular mortality (RR 0.85; 95% CI 0.71-1.01; p = 0.07). However, compared with placebo, GLP-1 RAs significantly decreased the incidence of all-cause mortality (RR 0.82; 95% CI 0.72-0.93; p < 0.0001), non-cardiovascular mortality (RR 0.77; 95% CI 0.63-0.95; p = 0.01), and myocardial infarction (RR 0.73; 95% CI 0.62-0.86; p < 0.0001). Additionally, patients receiving GLP-1 RAs experienced significant overall weight loss (- 8.53 kg; 95% CI - 12.38 to - 4.68; p < 0.0001) and improvements in lipid profiles, including lower levels of total cholesterol (- 0.77 %; 95% CI - 1.03 to - 0.50; p < 0.0001), triglycerides (- 6.78 %; 95% CI - 8.11 to - 5.46; p < 0.0001), low-density lipoproteins (- 2.85 %; 95% CI - 3.74 to - 1.96; p < 0.0001), and very low-density lipoproteins (- 4.47 %; 95% CI - 5.56 to - 3.38; p < 0.0001). GLP-1 RAs also significantly increased the incidence of any adverse events (RR 1.11; 95% CI 1.05-1.16; p < 0.0001), with no difference regarding the incidence of serious adverse events. However, gastrointestinal adverse events were significantly more frequent in patients receiving GLP-1 RAs, with a higher risk of any gastrointestinal adverse events (RR 2.83; 95% CI 1.86-4.3; p < 0.001), nausea (RR 2.70; 95% CI 2.18-3.33; p < 0.001), diarrhea (RR 1.97; 95% CI 1.68-2.31; p < 0.001), vomiting (RR 3.85; 95% CI 3.32-4.48; p < 0.001), and constipation (RR 2.35; 95% CI 1.94-2.85; p < 0.001) than in those receiving placebo.

In obese patients without diabetes, GLP-1 RAs demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, and effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.

PROSPERO identifier number: CRD42024498538.

Eating disorders (EDs) are a relatively uncommon yet salient concern for patients undergoing metabolic and bariatric surgery (MBS). This report aims to advance understanding of the complex relationship between EDs and MBS by highlighting recent empirical evidence and identifying areas for future research.

Little-to-no empirical evidence suggests that EDs be considered an absolute contraindication for MBS. However, a small subset of patients experience recurrent or emergent ED symptoms following surgery, invariably resulting in poorer postsurgical outcomes. Plausibly, a confluence of psychosocial and neurobiological mechanisms explains post-MBS ED symptoms. Accurate identification of MBS-related ED concerns is essential, with growing evidence suggesting structured postsurgical treatment may be optimal. Despite recent advances, more research on EDs in the context of MBS is needed, including rigorous mechanistic studies with long-term follow-up that clarify how predisposing factors interact to precipitate postsurgical ED symptoms. More work is also required to inform design and dissemination of targeted ED interventions for patients pursuing MBS.

This study compared cardiovascular outcomes associated with metabolic and bariatric surgery (MBS) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with obesity.

The TriNetX network was used to compare cardiovascular risk in adult patients with BMI ≥35 who underwent MBS with those who received GLP-1 RA therapy for ≥2 years. Primary outcome was cardiovascular disease (CVD), a composite of incident heart failure (HF), coronary artery disease (CAD), and cerebrovascular disease. Patient follow-up lasted up to 10 years.

MBS was associated with lower hazard of the primary composite outcome of CVD (HR, 0.54, 95 ​% CI, 0.49-0.60), and the secondary outcomes of incident HF (HR, 0.45, 95 ​% CI, 0.39-0.52), CAD (HR, 0.54, 95 ​% CI, 0.45-0.66), and cerebrovascular disease (HR, 0.64, 95 ​% CI, 0.53-0.77).

A lower risk of adverse cardiovascular outcomes was noted after MBS compared with GLP-1 RA therapy in patients with obesity.

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use has dramatically increased with expanded indications for weight loss. Delayed gastric emptying due to these medications can lead to residual food in the stomach, which can increase the risk of periprocedural aspiration during endoscopic procedures. The aim of this study is to document rates of gastric food retention and aspiration events during upper endoscopy in patients on GLP-1 RA.

A retrospective cohort study was performed including all patients who underwent upper endoscopic procedures at two hospitals during 2018-2023. Procedure abortion due to the presence of food was taken as primary study endpoint. The secondary endpoint was aspiration events in patients with food noted on endoscopy.

Out of a total of 32,275 total upper endoscopic procedures performed during the study period, 1179 procedures were performed in patients taking GLP-1 RAs (GLP-1 cohort). In total, 37 endoscopies (0.1%) were aborted due to retained gastric food; 7 patients (0.6%) in the GLP-1 cohort vs 30 patients (0.096%) in the non GLP-1 cohort (p < 0.01). There were no episodes of aspiration in patients with retained food.

In a large retrospective cohort, GLP-1 RA use did increase rates of gastric food retention during upper endoscopy, though the absolute risk was minimal. There were no aspiration events related to gastric food retention. Because of the small number of events, there were no clear modifiable risk factors for gastric food retention. This study supports the practice of individualized periprocedural management in patients on GLP-1 RA.

Metabolic and bariatric surgery has been well described in the existing literature to be an effective and safe modality for weight loss in patients with obesity. Recently, hypoabsorptive procedures such as one-anastomosis gastric bypass (OAGB), biliopancreatic diversion with duodenal switch (BPD-DS), and single-anastomosis duodenoileostomy with sleeve (SADI-S) have gained traction, particularly among patients with severe obesity. These procedures combine restrictive and hypoabsorptive mechanisms, resulting in significant and sustainable weight loss, especially in those with severe obesity and associated comorbidities. However, the risk of malnutrition and nutritional deficiency following these procedures has been a deterrent for surgeons in their adoption. This review evaluates the existing literature on the safety, efficacy, and long-term outcomes of OAGB, BPD-DS, and SADI-S. While these hypoabsorptive procedures represent highly effective options for treating obesity, the associated nutritional complications necessitate the need for long-term follow-up and supplementation and highlight the need for careful patient selection.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), also known as incretin mimetics, have significantly revolutionized the treatment of type 2 diabetes mellitus (T2DM) and obesity worldwide, far exceeding initial expectations regarding their global prescription. This class of medications has demonstrated weight losses of up to 20 % of baseline body weight. Beyond their proven benefits in T2DM and obesity, GLP-1RAs, as well as dual and triple agonists (GLP-1/GIP/glucagon), are being investigated for their effects on conditions such as metabolic-associated steatotic liver disease, various cardiovascular disorders, neurocognitive impairments, and certain addictions. These emerging effects appear to be linked not only to their metabolic action but also to their ability to modulate the chronic inflammatory state underlying these pathologies.

This narrative review article explores the complex interplay between obesity, osteoarthritis, and their associated inflammatory cascades, offering a deeper understanding of the underlying of mechanisms of inflammation and potential therapeutic interventions targeting both diseases. Through examination of the shared inflammatory pathway of obesity and osteoarthritis, our objective is to directly elucidate the relationship between these two conditions, highlighting the promising role of glucagon-like peptide-1 agonists in modulating inflammation and its therapeutic implications for patients with obesity and osteoarthritis.

With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the USA. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.

Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related and non-liver-related mortality were analyzed.

Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; p<0.0001), liver-related (3.3% vs. 14%; p<0.0001), and non-liver-related mortality (22.3% vs. 26.9%; p=0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR]=0.63; p<0.0001), liver-related (aHR=0.24; p<0.0001), and non-liverrelated (aHR=0.81; p=0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR=0.39; p<0.0001) whereas open surgeries were associated with higher overall mortality (aHR=1.24; p=0.022).

Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.

Bariatric surgery (BS) is an effective intervention for obesity and related metabolic disorders, significantly improving metabolic health and alleviating hormonal imbalances. However, it induces complex endocrine changes that can lead to dysfunctions, impacting the somatotropic, gonadal, thyroid, pancreatic, and adrenal axes. This review highlights the dual effects of BS on the endocrine system. A comprehensive review of peer-reviewed studies using PRISMA guidelines was conducted, focusing on human research evaluating pre and postoperative endocrine parameters. Studies were selected for their relevance and quality in elucidating the endocrine consequences of BS. BS restores growth hormone secretion and improves fertility but may disrupt insulin-like growth factor-1 recovery and sex hormone balance, leading to bone loss and catabolic states. Postprandial insulin hypersecretion can result in hyperinsulinemic hypoglycemia, with impaired counter-regulatory hormone responses. Secondary hyperparathyroidism and reduced bone density highlight additional risks. Changes in thyroid hormone levels have implications for both hypothyroid and euthyroid patients. These findings underscore the interplay between improved metabolic control and potential endocrine dysfunctions. The current evidence predominantly comprises association studies that may not be of quality for safe clinical decision-making, highlighting the need for high-quality research to establish causality and refine therapeutic strategies. Bridging knowledge gaps in the mechanisms underlying these changes is crucial to optimizing BS outcomes. A holistic approach integrating preoperative screening, individualized postoperative care, and targeted therapies is essential to mitigate complications while maximizing benefits.

Obesity is one of the greatest public health concerns in the United States and has reached an epidemic scope over the past few decades. Plastic surgery in patients with obesity has been linked to higher complication rates both before and after weight loss. This article discusses the evolution and landscape of antiobesity medications as they apply to plastic surgery. Although bariatric surgery has been effective in long-term treatment, new pharmacologic advances in glucagon-like peptide-1 agonists, such as semaglutide, have demonstrated promising effectiveness. These medications pose several unique challenges, particularly with regard to perioperative management and risk of weight regain after discontinuation. An understanding of these new pharmacologic agents is crucial for plastic surgeons, who treat patients with obesity.

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight loss and glycemic control. In addition, the present investigation explores recent clinical studies demonstrating the effectiveness of GLP-1 RAs in diabetic and nondiabetic populations, highlighting their potential in addressing obesity even in those without T2DM and describing probable benefits to cardiovascular health. Finally, our investigation outlines the importance of future research to further define the potential benefits of GLP-1 RAs.

Pre-optimization of obese patients prior to abdominal wall reconstruction (AWR) is essential in mitigating their increased preoperative risks. Traditionally diet, exercising, bariatric surgery are the tools typically prescribed for weight loss. The advent of glucagon-like peptide-1 agonists (GLP-1A) which stimulate insulin secretion and inhibit gastric emptying have improved the weight loss armamentarium. However, there is a limited amount of literature on GLP-1A effectiveness and postoperative outcomes in AWR patients. This study compares the efficacy of GLP-1A to Bariatric Surgery (BAS) in perioperative AWR patient.

A prospectively maintained database was retrospectively reviewed to identify all patients undergoing AWR at our institution between January 2021 and March 2024. We included patients who required GLP-1A or BAS for weight optimization prior to AWR. We excluded patients on GLP1-A or history BAS not performed for AWR preoptimization. Basic demographics such as age, sex, race, weight and BMI at initial clinic visit and at surgery were compared. Primary endpoints included time to surgery, time to bowel recovery and length of stay (LOS). Time to surgery was defined as the number of months between the initial clinic visit and AWR. Time to bowel recovery was defined as the number of days it took for the first postoperative bowel function. Secondary endpoints included standard 30-days postoperative variables. Nominal variables were analyzed using a Fisher exact test and continuous variables were analyzed with Student's T test.

35 patients were included in this study (GLP-1A: 17, BAS: 18). The GLP-1A cohort had a lesser BMI at the initial clinic visit (40.8 vs 43.4, p = 0.188). GLP-1A cohort made it to the operating room faster (9.1 months vs 13.5 months, p = 0.06) from the first clinic visit; and (7.9 months vs 9.7 months, p = 0.4) from initiation of weight loss intervention. Albeit losing less weight (14.9 kg vs 27.1 kg, p = 0.008) with a lesser reduction in the BMI (4.69 vs 9.23, p = 0.004). The GLP-1A cohort showed a non-significant elevated LOS (5.2 days vs 3.6 days, p = 0.25) and an increased ileus rate (17.6% vs 0%, p = 0.1). However, there were no differences noted in time to bowel recovery (2.9 days vs 3.1 days, p = 0.76).

GLP-1A is effective in optimizing patients needing weight loss before AWR. They shorten the timeline to AWR intervention and have comparable peri-operative outcomes to BAS patients.

Obesity is both a major risk factor for diabetes and a serious comorbidity of the condition. The twin epidemics of obesity and diabetes have spread globally over the past few decades. Treatment of obesity in patients with diabetes provides a host of clinical benefits that encompass virtually all body systems. Despite this, multiple lines of evidence suggest that the efficacy of most therapies for weight loss is significantly reduced among patients with diabetes. With this background, we summarize the evidence of a differential effect of lifestyle, pharmacological, and surgical treatments for obesity in patients with existing diabetes, and explore the potential mechanisms involved in this phenomenon. This information is then used to formulate strategies to improve weight loss outcomes for patients with diabetes.

To assess whether use of glucagon-like peptide-1 (GLP-1) receptor agonists before upper gastrointestinal endoscopy is associated with increased risk of pulmonary aspiration or discontinuation of the procedure compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

Cohort study.

Two deidentified US commercial healthcare databases.

43 365 adults (≥18 years) with type 2 diabetes who used a GLP-1 receptor agonist or SGLT-2 inhibitor within 30 days before upper gastrointestinal endoscopy.

The primary outcome was pulmonary aspiration on the day of or the day after endoscopy, defined using diagnostic codes. The secondary outcome was discontinuation of endoscopy. Risk ratios and corresponding 95% confidence intervals (CIs) were estimated after fine stratification weighting based on propensity score.

After weighting, 24 817 adults used a GLP-1 receptor agonist (mean age 59.9 years; 63.6% female) and 18 537 used an SGLT-2 inhibitor (59.8 years; 63.7% female). Among users of GLP-1 receptor agonists and SGLT-2 inhibitors, the weighted risk per 1000 people was, respectively, 4.15 and 4.26 for pulmonary aspiration and 9.79 and 4.91 for discontinuation of endoscopy. Compared with SGLT-2 inhibitor use, GLP-1 receptor agonist use was not associated with an increased risk of pulmonary aspiration (pooled risk ratio 0.98, 95% CI 0.73 to 1.31), although it was associated with a higher risk for discontinuation of endoscopy (1.99, 1.56 to 2.53).

In this comparative cohort study, no increased risk of pulmonary aspiration during upper gastrointestinal endoscopy was observed among adults with type 2 diabetes using GLP-1 receptor agonists compared with SGLT-2 inhibitors within 30 days of the procedure; however, GLP-1 receptor agonists were associated with a higher risk of discontinuation of endoscopy, possibly owing to a higher risk of retained gastric content. In the absence of evidence from randomized trials, these findings could inform future practice recommendations on the preprocedural protocol for patients requiring endoscopy.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, particularly in individuals with obesity and type 2 diabetes mellitus (T2DM). This meta-analysis aimed to compare the effectiveness of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on cardiovascular outcomes and mortality in patients with obesity. A comprehensive literature search was conducted in Medline, Embase, and Cochrane CENTRAL from inception to September 15, 2024. Four observational studies meeting the inclusion criteria were analyzed, comprising a total of 247,000 patients. The primary outcomes were major adverse cardiovascular events (MACE) and all-cause mortality. Random effects models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). The results showed that BMS was associated with a significantly lower risk of MACE compared to GLP-1RAs (RR: 0.71, 95% CI: 0.56-0.90, p = 0.004), indicating a 29% reduction in MACE risk. Additionally, BMS demonstrated a 25% reduction in all-cause mortality risk (RR: 0.75, 95% CI: 0.65-0.87, p < 0.0001). These findings suggest that BMS offers superior cardiovascular protection and improved survival outcomes compared to GLP-1RAs in obese patients. The observed benefits may be attributed to more significant reductions in body mass index (BMI) and improvements in metabolic parameters achieved through surgical intervention. However, the limitations of this study, including its observational nature and the limited number of included studies, underscore the need for further research, particularly randomized controlled trials (RCTs), to confirm these findings and guide clinical decision-making in obesity management.

Obesity is a disease of epidemic proportions in the United States and contributes to morbidity and mortality for a large part of the population. In addition, the financial costs of this disease to society are high. Lifestyle modifications are key to prevention and treatment but adherence and long-term success have been challenging. Bariatric surgery has been available and pharmacologic approaches, first developed in the 1950s, continue to be an option; however, existing formulations have not provided optimal clinical efficacy and have had many concerning adverse effects. Over the last decade, glucagon-like peptide-1 (GLP-1) receptor agonists, a novel group of medications for the treatment of type 2 diabetes, were found to produce significant weight loss. Several formulations, at higher doses, received FDA approval for the treatment of obesity or those overweight with weight-related co-morbidities. More hormone-based therapies were and are being developed, some with dual or triple-receptor agonist activity. Their use, however, is not without questions and concerns as to long-term safety and efficacy, problems with cost and reimbursement, and how their use may intersect with public health efforts to manage the obesity epidemic. This review will focus on the GLP-1 receptor agonists currently used for weight loss and discuss their pharmacology, pertinent research findings establishing their benefits and risks, issues with prescribing these medications, and a perspective from a public health point of view.

The introduction of injectable glucagon-like peptide-1 (GLP-1) receptor agonists such as Ozempic (Novo Nordisk, Plainsboro, NJ) and Wegovy (Novo Nordisk Inc.) has transformed weight loss in plastic surgery patients, often leading to excess skin and soft tissue amenable to body contouring procedures.

The aim of this study was to examine the relationship between injectable GLP-1 receptor agonist use and the growing need for body contouring surgeries, focusing on trunk and extremity procedures.

A retrospective analysis of the PearlDiver database (PearlDiver, Inc., Colorado Springs, CO) was conducted, examining prescription data for Ozempic, Wegovy, and liraglutide, and correlating these with body contouring procedures across 30 US states from 2011 to 2022. Multimodal statistics were used to compare surgery rates and assess dosage and time interval patterns among GLP-1 receptor agonist users and nonusers.

Significant correlations between GLP-1 receptor agonist use (881 Ozempic, 59 Wegovy, and 4655 liraglutide users) and increased body contouring surgeries were found. Ozempic showed weak correlations with brachioplasty (r = 0.23) and panniculectomy (r = 0.21), and Wegovy with breast procedures (r = 0.28), while liraglutide showed consistent correlations across surgeries. Time to surgery varied from 87 days (Wegovy) to 1018 days (liraglutide), with higher surgery rates among users (P < .01) and dose-related differences, especially in Ozempic and Wegovy users.

This study demonstrates a dose-dependent link between the use of GLP-1 receptor agonists and an increase in subsequent aesthetic body contouring surgeries, highlighting the need for surgeons to adapt to the merging of medicinal body transformation and aesthetic plastic surgery.

Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.

Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis.

This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1 months post-BRS. We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes.

Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity.

Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.

This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity.

Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese.

The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events.

The global prevalence of obesity has risen sharply during the past half-century, reaching pandemic proportions and creating a public health crisis. Obesity is a recognized risk factor for the development of diabetes, atherosclerosis, hypertension, hepatic steatosis, and many other cardiometabolic disorders with significant resultant morbidity and mortality. Though treatment of obesity can prevent or slow the progression of the aforementioned illnesses, efforts to help patients achieve reliable and sustainable weight loss have had limited success. Improving nutrition and increasing physical activity results in a host of health benefits; however, the weight loss achieved with lifestyle interventions alone is modest and difficult to sustain. Early attempts at medical and surgical treatment of obesity were plagued with adverse effects and complications. Moreover, these approaches failed to demonstrate long-term health benefits, even when weight loss was achieved. Recently, novel incretin-based therapies targeting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors have gained popularity because of their effectiveness in achieving substantial weight loss in patients both with and without diabetes. Following many successful clinical trials, there are now multiple GLP-1 receptor agonists and one dual GLP-1-GIP receptor agonist approved by the Food and Drug Administration for chronic weight management. Advancements in laparoscopic surgical technique and refinements in procedure selection have similarly improved the safety and efficacy of bariatric metabolic surgery for patients with obesity. In this review, we discuss the advantages and disadvantages of contemporary pharmacologic and surgical weight management strategies. We review the data regarding expected weight loss, glycemic control, cardiometabolic benefits, and potential adverse effects of various treatment approaches. As obesity rates continue to rise worldwide, it is imperative that clinicians keep these considerations in mind in order to better care for patients.

Changes in autonomic (ANS) and enteric nervous systems (ENS) may be involved in pathogenesis of obesity. We hypothesized that baseline autonomic and enteric parameters may predict outcomes of diverse obesity therapies.

We studied ANS and ENS physiology in 37 patients (8 male, 29 female, age 45 years, weight 129.7 kg) at 4 centers in patients undergoing medical (9: low-calorie diet) versus invasive (22: 16 sleeve, 6 bypass) and semi-invasive (6: 2 band, 2 high energy stimulation, 2 aspiration) weight loss therapies. Weight loss was reported as percent weight loss from baseline to latest values at 1 year and in some up to 5 years; classified as < or > /= 20% for each group. ANS testing included sympathetic adrenergic function by measuring reflex vasoconstriction and postural adjustment ratio. ENS was measured non-invasively using cutaneous low-resolution electrogastrogram.

Percent weight loss was greater with the invasive (28.5%) than semi-invasive (9.1%) or non-invasive low-calorie diet (4.4%) (p < .001). Percent weight loss at 1 year (and up to 5 years) corresponded to the adrenergic measure of postural adjustment ratio (r = .42, p = .012), total pulse amplitude at rest (r = .56, p < .001), and electrogastrogram standing-to-rest difference (r = .33, p = .056).

Baseline autonomic and enteric function measures correspond to percentage with loss in this pilot study using diverse weight loss methods. Autonomic and enteric profiling has potential clinical use for evaluation and treatment of obesity but needed larger controlled trials.

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management.

Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO).

The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO.

In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m2vs 9.0 kg/m2, p = 0.004; ASMMI: 6.2 kg/m2vs 7.2 kg/m2, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3.

MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.

Background/Objectives: Bariatric surgery is a central cornerstone in obesity treatment. We aimed to assess the impact of diabetes on the postoperative outcomes of bariatric surgery and compare three techniques: sleeve gastrectomy, Roux-en-Y, and gastric banding. Methods: We extracted data from the National Inpatient Sample (2015-2019) using ICD codes. The primary outcome was postoperative mortality. Secondary outcomes were major bleeding, atrial fibrillation, and acute renal failure. Results: Among patients who underwent sleeve gastrectomy, diabetes was associated with a higher adjusted risk of mortality (aOR 2.07 [1.36-3.16]), atrial fibrillation, and acute renal failure, but a similar risk of bleeding. Among patients who underwent Roux-en-Y, diabetes did not increase mortality and bleeding risk. Still, it was associated with a higher risk of atrial fibrillation and acute renal failure. Among patients who underwent gastric banding, diabetes was only associated with a higher risk of bleeding. When comparing the three techniques in diabetes patients, Roux-en-Y was significantly associated with higher mortality and acute renal failure risk when compared to the other procedures. Bleeding was more common in Roux-en-Y than in Sleeve. Conclusions: In total, diabetes is associated with worse postoperative outcomes in bariatric surgery, regardless of the technique. Among diabetes patients, Roux-en-Y was associated with the highest mortality and morbidity.

Transit bipartition (TB) emerges as a bariatric surgery alternative to Duodenal Switch (DS), emphasizing complete intestinal access and reduced malabsorption. By directly stimulating the distal ileum, TB promotes weight loss while preserving endoscopic duodenal access. This technique enhances anorexigenic hormones, aiding in satiety and weight loss, with lower malnutrition risks than DS. TB shows favorable short-term outcomes in weight management and comorbidity reduction, serving as a simpler, less malabsorptive option than DS. Nonetheless, long-term studies are essential for comprehensive efficacy assessment.

The purpose of this American Gastroenterological Association (AGA) Institute Rapid Clinical Practice Update (CPU) Communication is to review the available evidence and provide expert advice regarding the evolving management of patients taking GLP-1 receptor agonists prior to endoscopy.

This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in this field, and it reflects the experiences of the authors who are experts in bariatric medicine and/or endoscopy.

This review will examine the most current evidence for Metabolic and Bariatric Surgery (MBS) in the pediatric population, specifically in terms of weight loss outcomes and improvement in comorbid conditions and complications. Additionally, we compare surgical and non-surgical interventions, review current guidelines, and propose a stepwise evidence-based approach to the management of obesity in children.

MBS is a safe option for appropriately selected pediatric patients which leads to significant and sustained weight loss. This weight loss is associated with improvement of related comorbid conditions. Laparoscopic sleeve gastrectomy (LSG) has emerged as the procedure of choice with a better safety profile. Despite the evidence, very few adolescents undergo MBS. New pharmacologic agents specifically the GLP-1/GIP agents have shown early promise especially in patients under body mass index 40, but the long-term effects are unknown. MBS is an effective tool in the management of pediatric obesity, and its use has been recommended by professional societies. Early referral to a multidisciplinary obesity team can help identify appropriate patients.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.

Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) is associated with faster and more relevant skeletal muscle impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk of falls, frailty, overall quality of life, and mortality. PubMed/Medline, Scopus, Web of Science, and Google Scholar were searched for research articles, scientific reports, observational studies, clinical trials, narrative and systematic reviews, and meta-analyses to review the evidence on the pathophysiology of di-abetes-induced sarcopenia, its relevance in terms of glucose control and diabetes-related outcomes, and diagnostic and therapeutic challenges. The review comprehensively addresses key elements for the clinical definition and diagnostic criteria of sarcopenia, the pathophysiological correlation be-tween T2D, sarcopenia, and related outcomes, a critical review of the role of antihyperglycemic treatment on skeletal muscle health, and perspectives on the role of specific treatment targeting myokine signaling pathways involved in glucose control and the regulation of skeletal muscle metabolism and trophism. Prompt diagnosis and adequate management, including lifestyle inter-vention, health diet programs, micronutrient supplementation, physical exercise, and pharmaco-logical treatment, are needed to prevent or delay skeletal muscle deterioration in T2D.

The understanding of idiopathic intracranial hypertension (IIH) has evolved over the past few years. Previously, IIH was considered a disease exclusively affecting the neuro-ophthalmic axis, characterized by raised intracranial pressure, headache and papilloedema, and resulting in the risk of severe and permanent visual loss and life-changing disabling headaches. Recent advances have begun to redefine IIH as a probable metabolic disease involving a range of systemic manifestations. More than 95% of individuals affected by the disease are women of reproductive age with obesity. The incidence is rapidly rising and parallels the escalating worldwide obesity rates. Contemporary insights identify associations with insulin resistance, type 2 diabetes and a twofold increased risk of cardiovascular disease in excess of that driven by obesity alone. Adipose distribution in people with IIH, like that in other metabolic diseases, is preferentially centripetal and is associated with changes in intracranial pressure. Evidence now demonstrates adipose tissue dysfunction in people with IIH, involving transcriptional and metabolic priming for lipogenesis and weight gain. Hormonal perturbations are also observed, including a unique phenotype of androgen excess that promotes cerebrospinal fluid secretion. Knowledge of these additional disease features is driving research into novel therapeutic targets and altering the approach to multidisciplinary care.

Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles, and medication doses to optimise glycaemic control. Most clinical guidelines on the management of diabetes mellitus (DM) provide only broad principles on diabetes care, and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications consequently. Therefore, a proper understanding of the pathobiology, clinical situation, and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes care. With the aid of five unique cases of DM [(1) Medically managed type 2 diabetes mellitus (T2DM) with severe obesity; (2) Management of T2DM with unreliable glycated haemoglobin (HbA1c); (3) Obesity in a patient with type 1 diabetes mellitus (T1DM); and (4) Late diagnosis and subsequent management of monogenic diabetes and 5. Sudden worsening of well-controlled T2DM)] we elaborate on the importance of individualised diabetes care and the practicalities in these situations. The review also provides an evidence update on the management of different forms of DM to guide physicians in optimising the care of their patients in day-to-day clinical practice.