Prediabetes: Epidemiology, diagnosis, and management

Table 1 Main advantages, disadvantages, and clinical uses of tests for prediabetes screening and diagnosis

Test	Advantages	Disadvantages	Main purpose
OGTT	Reference standard for diagnosing IGT; detects post-load dysglycemia[1,117]	Time-consuming; requires fasting and at least 2 h of testing; multiple blood samples; affected by recent diet, acute illness, stress, and medications	Diagnose IGT; assess glucose tolerance; clarify borderline or inconclusive cases
FPG	Simple, inexpensive, widely available; requires only one blood sample[1,117]	May miss isolated IGT or post-load hyperglycemia; affected by short-term physiological variation, acute illness, and stress	Diagnose IFG; initial screening in routine practice
HbA1c	No fasting or timed glucose loading required; reflects glycemic exposure over past 2-3 month; relatively low short-term variability[1,23,24]	Affected by altered red cell turnover, hemoglobin variants, anemia, blood loss, kidney disease, pregnancy, HIV, and some medications	Screening and diagnosis according to specific guidelines; risk stratification and follow-up monitoring
CGM	Provides continuous glucose profiles; captures glycemic variability and postprandial excursions; avoids repeated venipuncture[27,28]	High cost and limited access; sensor-related discomfort; interstitial glucose may lag behind blood glucose; diagnostic thresholds for prediabetes are not standardized[28]	Mainly used in diabetes management; may be useful for research or selected high-risk individuals, but not routine prediabetes diagnosis

OGTT: Oral glucose tolerance test; IGT: Impaired glucose tolerance; FPG: Fasting plasma glucose; IFG: Impaired fasting glucose; HbA1c: Glycated hemoglobin; CGM: Continuous glucose monitoring; HIV: Human immunodeficiency virus.

Table 2 Comparison of selected guideline recommendations for prediabetes screening and pharmacological prevention

Guideline	Screening recommendation	Prediabetes/high-risk criteria	Pharmacological prevention
ADA 2026	Screen from age 35; earlier with overweight/obesity plus risk factors	FPG 5.6-6.9 mmol/L; 2-hour OGTT 7.8-11.0 mmol/L; HbA1c 5.7%-6.4%	Consider metformin in selected high-risk adults (age 25-59, BMI ≥ 35 kg/m2, higher glycemia, or previous GDM)
USPSTF 2021[118]	Adults aged 35-70 years with overweight/obesity	Prediabetes by FPG, HbA1c, or OGTT	Offer/refer to effective preventive interventions; metformin may benefit selected high-risk groups
NICE PH38[119]	Risk assessment, then FPG or HbA1c in people at increased risk	FPG 5.5-6.9 mmol/L or HbA1c 6.0%-6.4%	Consider metformin if lifestyle intervention is ineffective or not feasible, especially BMI > 35 kg/m2

ADA: American Diabetes Association; USPSTF: United States Preventive Services Task Force; NICE: National Institute for Health and Care Excellence; FPG: Fasting plasma glucose; OGTT: Oral glucose tolerance test; HbA1c: Glycated hemoglobin; BMI: Body mass index; GDM: Gestational diabetes mellitus.

Table 3 Effects of dietary interventions relevant to prediabetes on body weight, glycemic control, blood lipids, and sustainability

Diet	Key features	Body weight	Blood lipids			Blood glucose	HbA1c	Sustainability
			HDL-C	LDL-C	Triglycerides
Ketogenic diet	High-fat, very low-carbohydrate pattern; macronutrient composition varies, and classical regimens are often approximately 70% fat, 10% carbohydrate, and 20% protein[120]	Usually decreases in overweight/obese adults and in T2DM studies; evidence specifically in prediabetes remains limited[49,50,53,54]	Variable; may increase in some studies[53,54]	Variable; LDL-C may increase in some individuals and should be monitored[49,120]	Usually decreases[49,53,54]	May improve fasting or overall glycemia, mainly supported by T2DM and mixed dysglycemia studies[49,53,54]	May decrease in the short term; in Keto-Med, HbA1c reduction was not clearly superior to Mediterranean diet[49]	Restrictive pattern; long-term adherence may be challenging and may be lower than with the Mediterranean diet[49,51]
Mediterranean diet	Plant-based dietary pattern emphasizing vegetables, fruits, whole grains, legumes, nuts, olive oil as the main fat source, moderate fish intake, and limited saturated fat[57,121]	May support weight loss or weight maintenance when combined with energy control and lifestyle management[71,121,122]	May improve or maintain HDL-C[122]	Generally neutral or favorable, depending on baseline diet and fat quality[121-123]	May decrease[121,122]	Associated with improved glycemic control and lower diabetes risk in clinical and epidemiological studies[59,60,71,121-124]	May decrease; benefits are reported in T2DM and prediabetes-related studies[49,121,122]	Generally more compatible with long-term dietary practice than highly restrictive regimens[49,71]
PPT diet	Personalized postprandial glucose response-targeting diet based on individual-level data and machine-learning prediction[70]	Not primarily a weight-loss diet; modest decrease reported in some intervention studies without prescribed calorie restriction[72]	May improve, but evidence is limited and not consistently superior to Mediterranean diet[71,72]	No consistent advantage over Mediterranean diet has been established[71,72]	May decrease, but evidence remains limited[71,72]	Targets postprandial excursions; one prediabetes trial showed better reduction in postprandial hyperglycemia than Mediterranean diet[71]	Greater HbA1c reduction than Mediterranean diet was reported in one prediabetes trial[71]	Personalization may support adherence, but implementation depends on data collection, algorithm access, and patient engagement[70,71]

HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; HbA1c: Glycated hemoglobin; PPT: Personalized postprandial glucose response-targeting diet; T2DM: Type 2 diabetes mellitus.

Table 4 Pharmacological interventions for prediabetes

Drug category	Representative agents	Action profile	Applicable population	Potential limitations	Clinical implication
Biguanides	Metformin	Reduces hepatic glucose production and improves insulin sensitivity; possible intestinal effects[75]	High-risk prediabetes, especially younger adults, higher BMI, elevated fasting glucose or HbA1c, or previous gestational diabetes[74]	Less effective than intensive lifestyle intervention; preventive effect weakens over time[6,76]	Best-established option; suitable as an adjunct for selected high-risk individuals
α-glucosidase inhibitors	Acarbose, voglibose	Delay intestinal carbohydrate digestion and absorption; reduce postprandial glucose excursions[80]	Mainly IGT or postprandial dysglycemia[77,78]	Gastrointestinal adverse effects, meal-time dosing, adherence burden, and lack of clear cardiovascular benefit[79,80]	May delay diabetes onset in IGT-dominant prediabetes, but not generalizable to all forms of prediabetes
Thiazolidinediones	Rosiglitazone, pioglitazone	Improve insulin sensitivity through PPARγ activation	Selected high-risk non-diabetic populations with IFG or IGT[81,83,84,125]	Weight gain, edema, heart failure risk, fracture risk, hepatotoxicity or cardiovascular safety concerns[81,83,84,125]	Strong proof of concept for targeting insulin resistance, but safety concerns limit routine use
GLP-1 receptor agonists	Liraglutide, semaglutide	Promote weight loss, reduce appetite, delay gastric emptying, and regulate insulin and glucagon secretion[89]	Prediabetes with overweight or obesity[85-87]	Gastrointestinal adverse effects, injection burden, high cost, and partial loss of benefit after withdrawal[85,87,90]	Most relevant for obesity-related prediabetes; not routine therapy for all patients
GIP/GLP-1 dual receptor agonists	Tirzepatide	Activates GIP and GLP-1 receptors; associated with weight loss, reduced appetite, improved insulin secretion and insulin sensitivity[91]	Obesity with prediabetes[92]	Long-term injections, weight regain after withdrawal, gastrointestinal adverse effects, cost and access issues[92,93]	Promising for obesity-related prediabetes, but evidence should not be generalized to all prediabetic individuals
Other agents	Orlistat, SGLT2 inhibitors and selected non-core agents	Weight-loss related, cardiorenal-metabolic, insulin secretory, vascular-metabolic, or supplementation-based approaches[94-98]	Selected high-risk or disease-specific populations	Evidence is narrower or less consistent; some agents show limited or negative effects	Secondary or context-dependent options rather than core pharmacological strategies

DPP: Diabetes prevention program; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent insulinotropic polypeptide; PPARγ: Peroxisome proliferator-activated receptor gamma; SGLT2: Sodium-glucose cotransporter 2.

Table 5 Summary of metabolic and bariatric surgical procedures relevant to obesity-associated prediabetes

Procedure	Mechanism/nature	Potentially suitable population	Procedure summary	Main limitations or complications
RYGB	Combined restrictive and malabsorptive procedure	Patients with obesity and marked metabolic abnormalities; evidence in prediabetes is mainly derived from obesity cohorts or indirect T2DM data[30,100,101]	Creation of a small gastric pouch with jejunal anastomosis, bypassing the distal stomach, duodenum and proximal jejunum[102]	Nutritional deficiencies, anastomotic leak, hemorrhage, dumping symptoms, and need forlong-term follow-up[102,104,126]
LAGB	Restrictive procedure	Patients requiring a less invasive, adjustable, and reversible procedure; now less commonly used because of weaker long-term weight-loss and metabolic effects[106,108]	Placement of an adjustable silicone band around the upper stomach to create a small gastric pouch[106]	Band slippage, port-related problems, erosion, insufficient weight loss, band removal, or conversion to other procedures[106,127]
SG/VSG	Mainly restrictive procedure with metabolic effects	Commonly performed procedure; may be suitable for patients with obesity and prediabetes, although direct prediabetes evidence remains limited[30,110,111]	Resection of most of the stomach along the greater curvature, leaving a tubular gastric sleeve[109]	GERD, staple-line leak, bleeding, and possible nutritional deficiencies[109,110,112]
BPD/DS	Combined restrictive and strongly malabsorptive procedure	Mainly considered for severe or super obesity, especially BMI ≥ 50 kg/m2, or as a revisional option after insufficient response to other procedures[113-115]	Sleeve gastrectomy with preservation of the pylorus and intestinal bypass[115]	Higher risk of nutritional deficiencies, protein-calorie malnutrition, fat-soluble vitamin deficiency, diarrhea, malodorous flatus, anastomotic leak, and hemorrhage[115,116]

The evidence for several procedures is derived mainly from obesity or type 2 diabetes mellitus cohorts and should not be directly generalized to all individuals with prediabetes. RYGB: Roux-en-Y gastric bypass; LAGB: Laparoscopic adjustable gastric banding; SG/VSG: Sleeve gastrectomy/vertical sleeve gastrectomy; BPD/DS: Biliopancreatic diversion with duodenal switch; GERD: Gastroesophageal reflux disease; T2DM: Type 2 diabetes mellitus.