Early weight loss: a window of opportunity for long-term glycaemic control and remission

April 30, 2025 — 08:00 🕑 5 minutes

Early weight loss: a window of opportunity for long-term glycaemic control and remission

A recent study provides evidence that losing more than 10 % of body weight early after diabetes diagnosis can significantly improve longterm glycaemic control and increase remission rates. Based on up to 25 years of follow-up, the authors make the case for early intervention strategies.

Weight interventions have long been a cornerstone in type 2 diabetes management. While current Guidelines acknowledge that weight loss can be disease-modifying and can even lead to remission, the optimal extent and timing of weight loss remain unclear.

Previous studies such as Look AHEAD and DiRECT yielded promising results in terms of diabetes remission in the short term. However, glycaemic as well as cardiovascular benefits could not consistently be shown over a five-to-ten-year observation period.

A new retrospective study published in Diabetologia now revisits the weight loss question. The authors investigated the effect of a weight loss target of ≥10 % in the early years after type 2 diabetes diagnosis and how this might alter the disease course. The results show a clear difference in outcomes between those who achieved the target and those who did not.

The critical early phase

Looking back on 25 years of data, the authors found that early weight loss of ≥10 % in people with type 2 diabetes was associated with better glycaemic control and up to four times higher remission rates. “These findings enhance our understanding of how weight loss influences disease progression over a long run by emphasising the critical early period where the greatest benefits occur, supporting early intervention strategies,” says principal investigator Gian Paolo Fadini. He is Full Professor of Endocrinology at the University of Padova, Italy, as well as member of EASD and Programme Chair at the Scientific Board of the European Foundation for the Study of Diabetes (EFSD).

He adds: “Sustained weight loss is associated with long-term benefits in diabetes management. The study highlights a dose-response relationship between the extent of weight loss and improvements in metabolic markers.” Fadini stresses that early and sustained weight loss should be a key therapeutic goal for all people diagnosed with type 2 diabetes. In the long term, this can help achieve significant benefits.

Up to 25 years of follow-up

The retrospective non-interventional study investigated the benefits of weight loss in people with newly diagnosed type 2 diabetes (mean diabetes duration of less than 2 years). Two independent cohorts were analysed: cohort 1 included 1,934 people (after exclusions) with up to 25 years of follow-up; cohort 2 included 13,277 people with up to 10 years of follow-up.

The primary outcome was HbA1c, with secondary outcomes including remission rates, cardiovascular parameters, the number of glucose-lowering medications, and the likelihood of starting insulin. At baseline, mean HbA1c ranged from 57 to 64 mmol/mol (7.4–8.0 %), and mean body mass index was around 30 kg/m2. In cohort 1, 15.9 % of participants achieved a weight loss of more than 10 %; in cohort 2, 8.8 % achieved this goal.

Remission rates up to fourfold higher

When comparing those who lost <10 % and ≥10 % of their body weight, there was a clear divergence in the outcomes (Figure 1). Remission rates (Figure 1, right panels) were significantly higher in the ≥10 % weight loss group, reaching 20.2 % vs 5.5 % (Hazard ratio [HR]: 4.2) in cohort 1. A similar trend was seen in cohort 2, with remission rates of 13.2 % vs 4.1 % (HR: 2.6).

Regarding the primary outcome, HbA1c (Figure 1, middle panels), the extent of weight loss correlated with a faster reduction in glycaemic levels. In cohort 1, the adjusted mean difference between the two groups was 2.1 mmol/mol or 0.19 % (p < 0.001), and similar trends were observed in cohort 2. However, these effects were not consistent over the follow-up period, and Fadini notes: “The study urges caution in overstating the pathogenetic role of obesity as a cause of type 2 diabetes. In fact, even with long-term weight management, glycaemic control worsens over time, showing how diabetes pathophysiology goes far beyond excess weight.”

In addition to improvements in HbA1c and remission, those with greater weight loss also experienced improvements in systolic blood pressure, HDL cholesterol and triglycerides.

Figure 1: Change over time in body weight and HbA1c levels as well as remission rates compared between the < 10 % (blue) and ≥ 10 % (red) weight loss groups. In both cohorts, the two weight loss target groups differ significantly.

What clinicians should be aware of

The findings highlight the role of weight loss in early diabetes management. “Clinicians should prioritise structured weight loss programmes, particularly soon after diabetes diagnosis, to maximise glycaemic benefits. The study also suggests that tailored interventions focusing on long-term adherence may help sustain metabolic improvements and reduce complications,” Fadini points out.

However, he cautions: “At the same time, clinicians should be aware that weight loss per se may be insufficient to change the natural history of diabetes, if good glycaemic control or remission is not achieved.” While the study showed improvements in glycaemic outcomes, it found no direct association between ≥10 % weight loss and a reduction in complications. Instead, remission itself was independently linked to significantly fewer cases of new-onset microangiopathy. The conclusion: “Remission more than weight loss was associated with a reduced risk of complications.”

Why timing is everything

So why is the early period after diagnosis so important? “The pronounced glycaemic benefits in the early years are likely due to the restoration of beta cell function and improved insulin sensitivity following initial weight loss. Early weight reduction may reverse some of the metabolic dysfunction associated with diabetes, providing a ‘window of opportunity’ in which significant improvements can be achieved,” explains Fadini.

“Over time, however, the effects tend to plateau as the disease progresses and other physiological factors come into play. In particular, the loss of beta cell function, which is mainly determined genetically, seems to take over and drive an irreversible loss of glycaemic efficacy,” Fadini explains.

Setting the right target

These findings add to the existing knowledge about the impact of weight loss on the course of diabetes. Most importantly, they highlight the importance of having a high cut-off point for early weight loss targets and interventions that start immediately after diabetes diagnosis. However, some questions remain. “Future studies should explore the mechanisms underlying the diminishing glycaemic benefits over time and identify strategies to prolong these effects,” Fadini looks ahead.

Also, the optimal weight loss target for sustained diabetes remission still needs to be identified. For example, the study did not explore whether a cut-off of >15 might yield even greater benefits. As therapeutic options to achieve such substantial weight loss become more available, they should be accompanied by studies, says Fadini. “Additionally, future research should assess individualised approaches based on genetic, metabolic, and behavioural factors to enhance long-term adherence and efficacy,” he concludes.

As the link between weight and diabetes progression becomes clearer, identifying and seizing windows of opportunity — particularly regarding timing — becomes increasingly important.

Key Points:
In this study, early weight loss of ≥ 10 % was associated with better glycaemic control and up to four times higher remission rates in type 2 diabetes.
According to the authors, clinicians should prioritise structured weight loss programmes, especially soon after diabetes diagnosis, to maximise glycaemic benefits.
Early intervention may restore beta cell function and improve insulin sensitivity, providing a ‘window of opportunity’ to alter the course of type 2 diabetes.
Future studies should explore the optimal weight loss target and identify strategies to prolong the glycaemic benefits over time.

To read this paper visit: Morieri ML, Rigato M, Frison V, et al. Early weight loss, diabetes remission and long-term trajectory after diagnosis of type 2 diabetes: a retrospective study. Diabetologia. https://doi.org/10.1007/s00125-025-06402-w

Author: Hanna Gabriel, BA MSc. Any opinions expressed in this article are the responsibility of EASD e-Learning.

Early weight loss: a window of opportunity for long-term glycaemic control and remission

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