# A Longitudinal Multicenter Study Comparing the Effectiveness of Pharmacological and Lifestyle-Only Interventions in Adults With Prediabetes for Preventing Acute Hyperglycemic Crises and Progression to Type 2 Diabetes Mellitus

## TL;DR

This study compares how well medicine and lifestyle changes prevent prediabetes from becoming type 2 diabetes or causing severe blood sugar spikes.

## Contribution

The study provides new evidence on the comparative effectiveness of pharmacological versus lifestyle-only interventions in preventing prediabetes progression.

## Key findings

- Pharmacological therapy showed modestly better protection against progression to T2DM compared to lifestyle-only interventions.
- Both groups improved metabolic markers, but adherence was higher in the pharmacological group.
- Acute hyperglycemic crises were rare and not significantly different between the two groups.

## Abstract

Background: Prediabetes is a high-risk metabolic state that, if not effectively managed, can progress to type 2 diabetes mellitus (T2DM) or acute hyperglycemic crises. Early intervention is, therefore, critical to reduce the burden of diabetes-related morbidity.

Objectives: The primary objective of this study was to compare the long-term effectiveness of pharmacological therapy vs. lifestyle-only interventions in preventing the progression of prediabetes to T2DM. The secondary objectives were to assess the incidence of acute hyperglycemic crises, as well as the long-term adherence and metabolic improvements associated with each intervention strategy.

Methods: This multicenter, longitudinal cohort study was conducted at Lady Reading Hospital and Khyber Teaching Hospital in Peshawar from January 2022 to December 2024. A total of 1,520 adults with prediabetes (defined as fasting plasma glucose 100-125 mg/dL or glycated hemoglobin, HbA1c, 5.7%-6.4%) were enrolled and followed for 24 months. Participants were assigned to either a pharmacological intervention group (n = 760) receiving metformin (500-1,000 mg twice daily) or an alternative agent when contraindicated, alongside standard counseling, or a lifestyle-only group (n = 760) following a structured program including individualized dietary counseling, at least 150 minutes of moderate physical activity per week, and monthly follow-up sessions for motivation and monitoring. Exclusion criteria included known diabetes, severe renal or hepatic impairment, pregnancy, or current use of glucose-lowering agents. Pill counts and follow-up attendance records assessed adherence. Anthropometric parameters, glycemic indices, lipid profiles, and blood pressure were measured at baseline and at each six-month interval. The primary outcomes were progression to T2DM and occurrence of acute hyperglycemic crises. Secondary outcomes included adherence rates and adverse events. Statistical analyses were performed using IBM Statistical Package for the Social Sciences software (version 26). Repeated measures analysis of variance, Kaplan-Meier survival curves, and Cox proportional hazards regression were used to evaluate predictors of progression, with p < 0.05 considered significant.

Results: Both intervention groups demonstrated significant improvements in weight, body mass index, fasting plasma glucose, HbA1c, and lipid parameters over 24 months (p < 0.001 for all). Adherence was higher in the pharmacological group: 655 (86.1%) vs. 598 (78.7%); p = 0.004. Progression to T2DM occurred in 72 (9.47%) patients in the pharmacological group and 94 (12.37%) in the lifestyle-only group (p = 0.03). Acute hyperglycemic crises were rare: six (0.79%) vs. seven (0.92%), p > 0.05. The composite outcome of progression to T2DM or hyperglycemic crises was significantly lower in the pharmacological group: 78 (10.26%) vs. 101 (13.29%), p = 0.02. Adverse events were mild and manageable, primarily gastrointestinal intolerance.

Conclusion: Both pharmacological and lifestyle interventions effectively improved metabolic outcomes among adults with prediabetes. However, pharmacological therapy provided modestly greater protection against disease progression and relapse. While the findings highlight the clinical value of early pharmacologic intervention, results should be interpreted with consideration of adherence variability and potential center-level differences. Larger randomized studies are warranted to confirm these observations.