Weight loss with lorcaserin linked to improved glycemic profile
medwireNews: Losing weight in the CAMELLIA-TIMI 61 trial was associated with a significantly reduced risk for developing type 2 diabetes, the investigators have reported at the 54th EASD Annual Meeting in Berlin, Germany.
And among the 56.8% trial participants (of 12,000 in total) with type 2 diabetes at baseline, a median 3.3 years of lorcaserin treatment was associated with a significant 0.33% improvement in glycated hemoglobin (HbA1c) levels at 1 year relative to placebo. There were smaller, although still significant, decreases of 0.09% and 0.08% in patients with prediabetes (33.3% of the cohort) and normoglycemia (9.9% of the cohort), respectively.
The largest improvement, of 0.52%, occurred in patients with a baseline HbA1c higher than 64 mmol/mol (8.0%), reported investigator Erin Bohula (Brigham and Women's Hospital, Boston, Massachusetts, USA).
Taking lorcaserin reduced the risk for diabetes by 19% among patients with prediabetes in the intention-to-treat analysis, corresponding to a number needed to treat of 56 to prevent one case of diabetes over 3 years, show the findings, which are published in The Lancet.
However, during the presentation, the researchers and trial commentator agreed that the glycemic effects of lorcaserin are likely to be mostly or entirely due to its effects on weight loss, rather than any direct effects on glucose control.
For this reason, and given the existence of medications such as glucagon-like peptide (GLP)-1 receptor agonists, which directly affect glucose as well as promoting weight loss, Bohula told medwireNews that lorcaserin is unlikely to be used as a first-line medication in people with diabetes.
The only caveat, “and I think it’s a small caveat but it’s one to say,” is that there are no cardiovascular outcome trials specifically testing the higher GLP-1 doses used for weight loss, she said.
“Probably it will be fine,” she added, “but there is some sort of question, because they do increase heart rate, for example.”
Lorcaserin significantly reduced weight regardless of glycemic status, and in patients with diabetes this was not affected by whether they were taking diabetes medications that promoted weight gain or weight loss.
More patients with diabetes shifted to a state of prediabetes or normoglycemia with lorcaserin than placebo, fewer needed to intensify their diabetes medications, and more were able to discontinue medications. Taking lorcaserin was also associated with a reduced rate of new microvascular complications, driven entirely by a reduced risk for microalbuminuria.
“I think what’s going to happen in the real world is that people are going to use the GLP-1 receptor agonist, they’ll use the SGLT2 [sodium-glucose cotransporter 2] inhibitors, and then they may pile on top of that – if it’s an obese patient – some weight-loss agent,” said Bohula.
But she added that “we probably will never have the combined efficacy and safety data” for antidiabetic agents and weight-loss medications, so clinicians will prescribe both without being certain of the combined effects.
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