TOPLINE:

In adults with obesity and type 2 diabetes (T2D), a reduction in BMI during intentional weight loss was associated with a reduced risk for retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral artery disease (PAD), regardless of changes in A1c levels.

METHODOLOGY:

• This retrospective cohort study analysed real-world data to evaluate whether intentional weight loss reduced the risk for microvascular and macrovascular complications in 100,507 individuals with obesity and T2D (mean age, 53.3 years; 58% men; mean BMI, 35.8).
• Changes in BMI and A1c levels were measured over the 4-year weight-loss period.
• The primary outcome was the time to the first diagnosis of retinopathy, neuropathy, CKD, myocardial infarction (MI), PAD, or stroke; secondary outcomes focused on composite microvascular and macrovascular complications.
• The median follow-up duration, measured after the 4-year weight-loss period, was approximately 5 years.

TAKEAWAY:

• After the 4-year weight-loss period, the mean relative reduction in BMI was 2.2% from baseline, and the mean absolute change in A1c levels was 0.0% from baseline.
• Each 1% decrease in BMI was associated with a lower risk for retinopathy (hazard ratio [HR], 0.989), neuropathy (HR, 0.988), CKD (HR, 0.987), and PAD (HR, 0.994; P < .001 for all); no significant association was observed for MI or stroke.
• Every 1-percentage point decrease in A1c levels was linked to significant risk reductions across all primary outcomes, including MI and stroke.
• Reductions in both BMI and A1c levels were associated with a lower risk for composite microvascular and composite macrovascular complications.

IN PRACTICE:

"Overall, this study highlights the potential benefit of a combined approach to actively reduce both BMI and HbA1c [A1c] in people living with T2D to further reduce the risk of complications and healthcare system burden associated with the management of these conditions," the authors wrote.

SOURCE:

This study was led by Akshay Jain, MD, TLC Diabetes and Endocrinology, Surrey, British Columbia, Canada. It was published online on December 10, 2025, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

This study used retrospective data from routine care, which often had missing or incorrect entries and inconsistent documentation across settings. The requirement for both a baseline and a 4-year BMI and A1c record likely introduced selection bias towards higher-risk or more closely monitored patients. Uncertainty may have existed, particularly at higher magnitudes of weight loss.

DISCLOSURES:

This study was funded by Novo Nordisk. Four authors reported being employees of Novo Nordisk A/S. One author reported receiving grants/research support from multiple companies; speakers bureau/honoraria from numerous organisations, including WebMD; and consulting fees from several companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.