Adults with overweight or obesity and type 2 diabetes who are given the sodium glucose cotransporter 2 (SGLT-2) inhibitor drug dapagliflozin alongside moderate calorie restriction achieve much higher rates of remission compared with calorie restriction alone, finds a trial published by The BMJ today.
The researchers say this study provides a practical strategy to achieve remission for patients with early type 2 diabetes.
Type 2 diabetes affects over 400 million adults worldwide. It's not necessarily a permanent condition and can be reversed by intensive weight management, but the most effective methods of weight loss, such as a very low energy diet or bariatric surgery, are not easy to implement.
As well as helping to lower blood sugar levels, SGLT-2 inhibitors can also lead to weight loss, but their effect alongside calorie restriction on diabetes remission has not yet been investigated in a randomised controlled trial.
To address this, researchers carried out a trial involving 328 patients with type 2 diabetes of less than six years' duration at 16 centres in mainland China from 12 June 2020 to 31 January 2023.
Participants were aged 20-70 years with a body mass index (BMI) greater than 25 and were not taking any anti-diabetic medication other than metformin.
After excluding patients with a range of pre-existing conditions, a history of gastric surgery, and those taking weight loss drugs, participants were randomly assigned to either moderate calorie restriction (a reduction of 500-750 kcal/day) with dapagliflozin 10mg/day or placebo for 12 months.
All participants received dietary counselling throughout the trial, were asked to keep a dietary log, and were encouraged to be physically active (150 minutes of brisk walking every week or more than 10,000 steps per day).
Diabetes remission was defined as maintaining normal blood sugar levels for at least two months after stopping anti-diabetic medication.
At 12 months, 44% of participants in the calorie restriction plus dapagliflozin group were in remission compared with 28% in the placebo group, and there was a significantly greater reduction in body weight and insulin resistance in the dapagliflozin group. The results also showed benefits of dapagliflozin on body fat mass, systolic blood pressure, and cholesterol levels.
No significant differences in adverse events were seen between the two groups.
The researchers acknowledge some trial limitations. For instance, their findings cannot be generalised to patients with type 2 diabetes for more than six years or to other races or ethnic groups, and total energy expenditure was not assessed.
However, they say the structured dietary programme was practicable and feasible in a clinical setting and participants had good adherence to the combination of SGLT-2 inhibitor and moderate calorie restriction. Results were also similar after further analysis, suggesting that they withstand scrutiny.
As such, they conclude: "Our multicenter, double blind and randomised trial showed that the combined regimen of dapagliflozin and regular calorie restriction was effective in achieving remission of diabetes, lowering body weight, and improving metabolic risk factors among overweight or obese patients with type 2 diabetes."
This combined strategy is effective but questions remain, say UK researchers in a linked editorial. For example, should such glucose lowering drugs be discontinued at the point of remission, and can specific drug mechanisms be harnessed for a more individualised approach to remission of type 2 diabetes?
Despite these uncertainties, they note that SGLT-2 inhibitors are now co-first line drugs (with metformin) for many patients with type 2 diabetes. "This study supports more research into combined approaches to achieving successful and sustainable remission of type 2 diabetes," they conclude.
