Prediabetes: Epidemiology, diagnosis, and management

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.