SGLT-2 Inhibitor/GLP-1 Agonist Doubles Weight Loss in Diabetes

April 01, 2015

A small UK study suggests that adding a sodium glucose cotransporter 2 (SGLT-2) inhibitor to therapy for type 2 diabetes patients who are already taking a glucagonlike peptide 1 (GLP-1) agonist can result in additive weight loss.

The results of the retrospective, systematic case-note audit were reported by Andrew P McGovern, MD, of the Beta Cell Centre for Diabetes, Chelsea and Westminster Hospital, London, United Kingdom, at the recent Diabetes UK Professional Conference.

Although there were a proportion of patients, around 25%, who didn't lose any weight, among the "responders" there was twice as much weight loss in those taking both agents compared with those taking just one of the medications, Dr McGovern said.

Asked to comment, session chair Martin Rutter, MD, FRCP, of the Manchester Diabetes Centre, United Kingdom, said: "I don't think the data are really surprising; it's what you might expect. We have to acknowledge the limitations: a small study in a single center, and it's a retrospective case review, so we really do need data from the large databases, like [the Clinical Practice Research Datalink]," to confirm any such findings.

And Dr Rutter told Medscape Medical News: "Weight change is not the primary reason people start these agents; it's important to stress that. These are glucose-lowering drugs, and the benefits as far as weight is concerned are secondary — we are not in a position at the moment to prescribe [them] for weight per se."

"A Reasonably Convincing Trend"

Dr McGovern explained that SGLT-2 inhibitors are type 2 diabetes drugs with an action independent of insulin, whereas GLP-1 agonists are "insulin dependent."

Both seem to invoke weight loss as a secondary outcome, but it is not known whether this is additive, given the differing mechanisms of action of the two drug classes.

In this small real-world observational study, he and his team identified all patients started on the SGLT-2 inhibitor dapagliflozin (Forxiga, Astra Zeneca/Bristol-Myers Squibb) — 122 were identified from electronic health and paper records. They then analyzed those with weight follow-up data, which included 88 patients — 48 of whom were on dapagliflozin with no GLP-1 agonist and 40 of whom had dapagliflozin added to a regimen that already included a GLP-1 agonist.

The GLP-1 agonists were liraglutide (Victoza, Novo Nordisk) in the case of 34 patients, exenatide (Byetta, AstraZeneca/Bristol-Myers Squibb) in five, and lixisenatide (Lyxumia, Sanofi) in one patient.

The mean duration of follow-up was 154 days: the mean weight change with dapagliflozin alone was -1.4 kg, whereas with the two agents was -2.8 kg (P = .05).

Some people did not lose any weight, however: 12 (25%) of those taking dapagliflozin alone and nine (23%) of those taking both agents.

But there was some heteroscedasticity, whereby a section of patients lost a lot of weight, Dr McGovern explained.

Among these responders, weight loss was -7.2 kg among those taking dapagliflozin and a GLP-1 agonist compared with -3.0 kg for those on dapagliflozin alone (P = .02), a "trend that is reasonably convincing," he observed.

Improvement in glucose control and blood pressure was comparable in both groups.

"These early data suggest that there are additive weight-loss effects of dapagliflozin and GLP-1 agonists," Dr McGovern said. "It will be really interesting to see — as we get more data — how this pans out and whether it's an ongoing effect," he concluded.

Dr Rutter said he would like to see a large clinical trial using this combination of agents to look at weight loss as a secondary outcome to glycemic control.

One GLP-1 agonist, liraglutide, has already been approved for use as a weight-loss agent in the European Union and the United States, albeit in higher doses than are used for type 2 diabetes.

Dr Rutter reports receiving grant support from Merck, Sharpe, and Dohme.

Diabetes UK Professional Conference. March 11–13, 2015; London, UK. Abstract A6 (P143).

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