Prediabetes in India: Sugary Iceberg and Place of Metformin to Mitigate it

India has an estimated weighted prevalence of prediabetes of 15.3% overall, making it a major contributor to the brunt of non-communicable diseases (NCDs) (1). Reportedly, a total of 45.1% of normal glucose tolerance (NGT) patients experienced a conversion to dysglycemia (as per defined criteria of prediabetes or diabetes); with 19.4% developing diabetes and 25.7% developing prediabetes (2).

Patients with prediabetes suffer clinical repercussions as a result of missed opportunities to prevent diabetes, raising the burden of complications on patients as well as the healthcare community (3). The distinct characteristics of the Indian population, which include a low body mass index (BMI), a high rate of insulin resistance, a young age at which diabetes onset occurs, and lower thresholds for diabetes risk factors make primary prevention of the disease more critical and desirable in India (4).

Prediabetes and Association of Vascular Complications & Beyond

Prediabetes is associated with a higher incidence of acute coronary syndrome, ischemic stroke, and heart failure. (5) Data from meta-analyses of 95 population-based cohort studies in adults revealed the positive association of prediabetes with risk for incidence of cardiovascular outcomes, coronary heart disease, stroke, chronic kidney disease, cancer and dementia (6). To prevent prediabetes from developing into diabetes and to lower the risk of micro- and macrovascular complications, early detection and interventions become crucial (3).

Early Screening Tools for Prediabetes in India

The diagnostic threshold for prediabetes as per the American Diabetes Association (ADA) is impaired fasting glucose (IFG) 100-125 mg/dL (5.6 and 6.9 mmol/L) and HbA1c 5.7-6.4% [39 and 47 mmol/mol] (2). The International Diabetes Federation (IDF) Position Statement released in 2024 emphasised that the 1-h post-load plasma glucose ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D (7).

The Madras Diabetes Research Foundation-Indian Diabetes Risk Score (MDRF-IDRS) is a practical and affordable instrument for early mass disease screening in primary public healthcare settings. Age, waist circumference, regular exercise, and family history were the four basic variables utilized by the MDRF-IDRS to classify people into three risk categories: high risk (score ≥60), moderate risk (scoring 30–50), and low risk (score <30) out of a possible total score of 100 (8). A study by Sengupta et.al., confirmed and validated the MDRF-IDRS as a valid simple and reliable screening tool to identify prediabetes in India with an accuracy area under an ROC (receiver operating characteristics) curve of 0.832 (95% confidence interval: 0.77–0.88). The study also highlighted that the MDRF-IDRS score equal to 60 or above had the highest sensitivity and specificity to identify prediabetes (9).

Benefits of Interventions in Improving Prediabetes Outcomes- Lessons from DPP Program

The Diabetes Prevention Program (DPP) research group carried out secondary analyses to examine the impact of metformin, lifestyle, and placebo interventions on the incidence of diabetes, which was defined as having an HbA1c of 6.5% or above. Metformin significantly reduced the incidence of diabetes by 38% vs 29% with lifestyle throughout the 10-year follow-up. This suggests that lifestyle and metformin are with metformin having greater efficacy in preventing diabetes (10).

Metformin reduced the risk of T2D in Indian Patients with Impaired Glucose Tolerance:

A meta-analysis and systematic review by Patel Dhara et.al assessed metformin's efficacy, safety, and long-term results using 17 randomized controlled trials, with a total sample size of 30,474 patients. Metformin showed lower odds of developing T2D by 35% in prediabetes patients compared to placebo and standard lifestyle interventions including diet and physical activities (0.65 odds ratio, 95% CI 0.53-0.80). Metformin also lowered the risk of developing T2DM by 42% compared to those in non-metformin intervention groups. (0.58 odds ratio, 95% CI 0.44-0.77). These findings provide strong evidence for the effectiveness of metformin in preventing the progression of prediabetes to T2DM and reducing the overall incidence of the disease (11).

Metformin- DCGI Approved Treatment for Prediabetes in India

In India, the Drug Controller General of India (DCGI) approved the use of metformin for the prevention or delaying of T2D. Metformin is indicated for the prevention of T2D. It should be considered in those with prediabetes, especially with BMI >35 kg/m2, aged above 60 years, women with prior gestational diabetes mellitus, and where lifestyle interventions are insufficiently effective in reducing body weight and improving glucose tolerance (2).

Metformin is the only drug treatment available for prediabetes and is beneficial for glycemic hygiene, vascular hygiene, and vasculo-metabolic hygiene (2).

Key Takeaways

• Prediabetes is a major health burden associated with an increased risk and brunt of subclinical metabolic & vascular sequels.
• The metabolic aberrations that lead to diabetes, its complications, and other related co-morbidities are chronic, requiring costly long-term interventions.
• Indian Diabetes Risk Score(IDRS) is a scientifically validated tool for prediabetes, predicting the risk of developing diabetes in the Indian population.
• Studies have shown that it is possible to prevent diabetes in native Asian Indian subjects with impaired glucose tolerance using an integrated approach including lifestyle modifications and metformin.
• The DCGI has approved metformin use in patients with prediabetes for the prevention and delaying of T2D.

Reference:

1. Anjana, Ranjit Mohan et al. “Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).” The lancet. Diabetes & endocrinology vol. 11,7 (2023): 474-489. doi:10.1016/S2213-8587(23)00119-5

2. Das AK, Mohan V, Ramachandran A, et al. An Expert Group Consensus Statement on “Approach and Management of Prediabetes in India”. J Assoc Physicians India 2022;70(12):69–78.

3. Chawla, R. Don’t let the “Pre” of Prediabetes fool you!. Int J Diabetes Dev Ctries 43, 845–846 (2023). https://doi.org/10.1007/s13410-023-01276-3

4. Ramachandran, A et al. “The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).” Diabetologia vol. 49,2 (2006): 289-97. doi:10.1007/s00125-005-0097-z

5. Nanavaty, Dhairya et al. “Prediabetes is an incremental risk factor for adverse cardiac events: A nationwide analysis.” Atherosclerosis plus vol. 54 22-26. 14 Sep. 2023, doi:10.1016/j.athplu.2023.08.002

6. Schlesinger, Sabrina et al. “Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies.” Diabetologia vol. 65,2 (2022): 275-285. doi:10.1007/s00125-021-05592-3

7. Bergman, Michael et al. “International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes.” Diabetes research and clinical practice vol. 209 (2024): 111589. doi:10.1016/j.diabres.2024.111589

8. Khan, Mohammad Mustufa et al. “Validity of Indian Diabetes Risk Score and its association with body mass index and glycosylated hemoglobin for screening of diabetes in and around areas of Lucknow.” Journal of family medicine and primary care vol. 6,2 (2017): 366-373. doi:10.4103/2249-4863.220010

9. Sengupta, Bitan, and Himadri Bhattacharjya. “Validation of Indian Diabetes Risk Score for Screening Prediabetes in West Tripura District of India.” Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine vol. 46,1 (2021): 30-34. doi:10.4103/ijcm.IJCM_136_20

10. Diabetes Prevention Program Research Group. “HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: a randomized clinical trial.” Diabetes care vol. 38,1 (2015): 51-8. doi:10.2337/dc14-0886

11. Patel, Dhara et al. “The Effectiveness of Metformin in Diabetes Prevention: A Systematic Review and Meta-Analysis.” Cureus vol. 15,9 e46108. 28 Sep. 2023, doi:10.7759/cureus.46108