Proactive Consideration of Metformin in Prediabetes-A Call of Action

Dr. Sanjay Kalra, MD and DM (Endocrinology), is the founder of Bharti Research Institute of Diabetes & Endocrinology, Karnal, Haryana. He is an Executive Editor of the Indian Journal of Endocrinology & Metabolism and Editor-in-Chief of the International Journal of Clinical Cases & Investigations.

Below are the key messages from this scientific meeting:

• Pre-Diabetes Is A Growing Epidemic With Regional Variations Across India: ICMR-INDIAB data show that pre-diabetes is now more prevalent than diabetes, and alarming trends in IFG and IGT suggest that up to one in ten may develop IFG and one in six could have IGT in the coming decades.
• Pre-Diabetes Is Not A Benign or Silent Stage: Even without progressing to diabetes, prediabetes is associated with insulin resistance, dyslipidemia, atherosclerosis, retinopathy, and neuropathy. Epidemiological data show a 6% increased risk of stroke, 10% for coronary heart disease, and 13% for both overall CVD and all-cause mortality.
• Diagnostic Criteria Are Clear, But Clinical Inertia Hampers Early Action: Pre-diabetes is defined by HbA1c levels between 5.7% and 6.4%, fasting plasma glucose of 100–125 mg/dL (IFG), or 2-hour OGTT values of 140–199 mg/dL (IGT). Healthcare providers often overlook marginal elevations in glucose or HbA1c. Dr. Sanjay Kalra emphasized tackling this inertia by focusing on three pillars: “awareness, articulation, and action.”
• Pre-Diabetes Is A Critical Intervention Window, Especially In Younger, Undiagnosed Individuals: Around two-thirds of individuals with dysglycemia fall into the pre-diabetic category, many are young and unaware. With proper education and support, many can adhere to lifestyle and pharmacologic interventions to halt disease progression and reduce complications.
• Lifestyle Modifications Are Essential But Impractical In Real-World: While foundational, lifestyle changes require sustained resources such as trained personnel, home visits, and structured programs. These limitations need to be factored while considering pharmacological treatment early, making metformin a more feasible and effective option, especially in underserved or resource-constrained populations.
• Metformin- Approved for Use in Prediabetes in 65 Countries: Metformin is the first-line pharmacologic agent for pre-diabetes and early diabetes, particularly in patients with high cardiovascular risk, obesity, metabolic syndrome, dyslipidemia, or rapid glycemic rise. Approved by the DCGI for pre-diabetes at the 500 mg SR dose, metformin is guideline-recommended when lifestyle measures are inadequate, starting at 250–500 mg BD. It is especially suited for individuals with IFG, IGT, or HbA1c 5.7–6.4%. High-risk groups include those with obesity, NAFLD, PCOS, GDM, HIV, HBV, syphilis, OSA, steroid use, or recurrent infections like balanoposthitis or pruritus vulvae. Its role spans:
• Primary prevention – delay or prevent T2DM onset
• Secondary prevention – halt pre-diabetes progression
• Primordial prevention – reduce vascular risk via vasculo-protective effects.
• Early Intervention with Lifestyle Modification and Metformin Improves Outcomes: Evidence from the DPP, DPS, IDPP (India), and D-CLIP studies shows that early intervention—lifestyle modification and metformin when indicated, within the first 6–12 months of diagnosis—significantly reduces the risk of diabetes and its complications. When lifestyle measures alone are insufficient, metformin should be added and continued, even if glycemic improvement occurs, to improve the trajectory of the disease. A maintenance dose of 250 mg BD is recommended to mitigate the early GI intolerance.
• Metformin: Benefits, Safety, and Broader Utility: Metformin is affordable, widely accessible, and has a favorable safety profile. It does not cause hypoglycemia or weight gain, and GI side effects are typically mild and transient. It is safe in moderate renal impairment, initiable at eGFR ≥30 mL/min/1.73 m² and continuable down to 15 mL/min/1.73 m². Beyond glycemic control, it offers anti-inflammatory and vasculo-protective benefits, with emerging evidence benefiting patients with dementia, OSA, and NAFLD. In PCOS, it improves insulin sensitivity, menstrual regularity, fertility, and weight; its use extends into pregnancy, including GDM, with potential embryo-protective effects. Dr. AK Das emphasized “If you ask me about pre-diabetes to diabetes, metformin is the numero uno drug, the molecule of the decade.”
• Community Screening-Awareness, Articulation & Action Enabling Intervention Are The Need Of The Hour: Opportunistic and targeted screening, such as testing relatives of diabetes patients and including HbA1c or OGTT in routine checkups, is crucial, especially in those with comorbidities. Women with GDM or pregnancy-related hyperglycemia, equivalent to prediabetes, must be prioritized, as early intervention benefits both mother and child long-term. Clinicians are encouraged to adopt a respectful and positive counselling language when communicating with patients.

Abbreviations: IFG – Impaired Fasting Glucose, IGT – Impaired Glucose Tolerance, ICMR-INDIAB – Indian Council of Medical Research – India Diabetes Study, HbA1c – Hemoglobin A1c, OGTT – Oral Glucose Tolerance Test, DCGI – Drug Controller General of India, BD – Bis in Die (Twice Daily), NAFLD – Non-Alcoholic Fatty Liver Disease, PCOS – Polycystic Ovary Syndrome, GDM – Gestational Diabetes Mellitus, HIV – Human Immunodeficiency Virus, HBV – Hepatitis B Virus, OSA – Obstructive Sleep Apnea, T2DM – Type 2 Diabetes Mellitus, eGFR – Estimated Glomerular Filtration Rate, DPP – Diabetes Prevention Program, DPS – Diabetes Prevention Study, IDPP – Indian Diabetes Prevention Program, D-CLIP – Diabetes Community Lifestyle Improvement Program