Sugary Iceberg of Prediabetes and Metformin's Role in Preventing Progression to T2D: Latest Meta-Analysis

Metformin reduced the risk of progression to diabetes by 22% in a large population of high-risk individuals with prediabetes, a new meta-analysis published by Indian authors has reported.

The findings of this research have been published in the latest issue of Clinical Diabetology 2024. The systematic review and meta-analysis included the largest number of studies to date to compute a summary effect size; and was carried out to analyze the effectiveness of metformin in delaying the progression of pre-diabetes to type 2 diabetes, the authors noted.

Study Overview:

The meta-analysis included 8869 patients with pre-diabetes, with 4328 patients in the metformin arm and 4541 patients in the control arm [lifestyle modification /placebo]. Random-effects model, with relative risk (RR) as the effect size and prediction interval (PI) was used as the indicator of heterogeneity. The RR was calculated by comparing the metformin and the control arm [lifestyle modification/placebo]. The dose of metformin varied across the trials, ranging from 500 mg per day to 1700 mg per day. The mean duration of follow-up ranged between 12–36 months.

Key Results:

The result showed a 22% relative risk reduction with metformin compared to lifestyle modification or placebo, with a 95% confidence interval of 0.71–0.86. The analysis also showed that the dose of metformin (low versus high) did not influence the outcome (p = 0.39).

Early Intensive Control with Metformin Improves Long-term Outcomes: Glance at Latest 2024 Published UKPDS 91 (2)

The findings of this analysis are along favourable lines regarding early intervention with metformin; with the results of a landmark trial, ‘United Kingdom Prospective Diabetes Study (UKPDS)’, with the longest-running follow-up for up to 42 years, wherein an early intensive glycemic control with metformin therapy, compared with conventional glycemic control (primarily diet), showed overall relative risk reductions of 20% (95% CI 5–32; p=0·010) for death from any cause and 31% (12–46; p=0·003) for myocardial infarction.

Practical Challenges and Role of Metformin

Lifestyle modification aiming at weight loss and reduction in insulin resistance has been the predominant strategy for preventing the transition from prediabetes to type 2 diabetes. However, achieving the required weight loss for metabolic benefits is difficult to achieve; and, more importantly, to sustain. Medications capable of inducing weight loss and improving insulin resistance are clinically useful. Metformin stands out as the most promising agent given its effect on weight and insulin resistance; as well as a favourable risk-benefit-cost effectiveness index. Given this background, the Drug Controller General India (DCGI) approved the use of metformin for the prevention or delaying of type 2 diabetes in prediabetes. The drug is suggested for use among individuals with prediabetes with body mass index (BMI) above 35 kg/m2, age above 60 years, women with prior gestational diabetes mellitus and where lifestyle intervention is insufficiently effective in reducing body weight and improving glucose tolerance.

References:

1. Samit Ghosal, Surekha Tippisetty, Subhadra Polisetti, Krishna G. Seshadri. Metformin for the Prevention of Prediabetes Progression to Type 2 Diabetes: A Systematic Review and Meta-Analysis. Clinical Diabetology 2024, DOI: 10.5603/cd.99821

2. Amanda I Adler, Ruth L Coleman, Jose Leal, William N Whiteley, Philip Clarke, Rury R Holman. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91). 2024 https://doi.org/10.1016/ S0140-6736(24)00537-3