Adaptive glycosuria response with SGLT2 therapy holds potential for weight loss

An adaptive increase in energy intake occurs with chronic glycosuria, especially in patients who are leaner with preserved renal function, according to research presented at the 50th European Association for the Study of Diabetes Annual Meeting.

These findings, from a study involving patients with type 2 diabetes, suggest combining treatment with sodium-glucose cotransporter 2 inhibitors with strategies to maintain that energy intake or curb appetite could be an avenue for weight loss, according to researchers.

“Weight loss in patients treated with SGLT2 inhibitors is consistently inferior to what is predicted by the glycosuria,” Giulia Ferrannini, MD, of the University of Pisa, Italy, said. “The discrepancy implies that a substantial increase in energy intake is part of the compensatory response to glycosuria.”

Ferrannini and colleagues analyzed data from 86 patients (39 women; age, 58 ± 9 years; BMI, 29.8 ± 4.5 kg/m²; HbA1c, 7.8 ± 0.8%; fasting plasma glucose,169 ± 41 mg/dL; estimated glomerular filtration rate, 89 ± 19 mL/min/1.73m²).

The patients received empagliflozin 25 mg/day (Jardiance, Boehringer Ingelheim) for 90 weeks. Body weight, FPG, eGFR and serum creatinine were assessed at timed intervals.

The researchers calculated time-dependent glucose filtration as the product of FPG and eGFR. Based on previous direct measurements, time-dependent urinary glucose excretion (UGE) was estimated, assuming a quasi-linear relationship between fractional UGE and glycemia. The researchers used a mathematical model simulating time-course of weight loss for a given change in calorie balance to approximate the relation of calorie-to-weight changes.

“We had two sets of data in the end — the observed changes in weight, body fat percentage and energy balance, and the expected,” Ferrannini said.

At 90 weeks, weight loss averaged –3.2 ± 4.2 kg (range, –17 to 5.5 kg). During 90 weeks, the average UGE was 54 ± 15 g/day (fractional UGE, 45 ± 4%).

Weight loss corresponded to a calorie deficit of –78 ± 103 kcal/day. Conversely, the observed calorie loss (–217 ± 59 kcal/day) predicted a weight loss of –8.7 ± 2.4 kg (range, –4 to –15.3 kg) during the study. Patients lost 38 ± 53% of the weight predicted by their glycosuria.

Patients’ energy intake likely rose (estimated +138 ± 116 kcal/day) based on previous studies demonstrating Excess calorie intake showed an inverse relation to baseline BMI (P<.01) and positive relation to baseline eGFR (P<.01).

Looking at patients who were treated with metformin vs. drug-naive, the researchers discovered weight loss was greater with therapy regardless of sex.

“The compensation may be partially offset by previous treatment with metformin,” Ferrannini said. “This is presumably because metformin has a restraining effect on appetite itself.”

For more information:

Ferrannini G. Abstract #3. Presented at: 50th EASD Annual Meeting; Sept. 16-19, 2014; Vienna.

Disclosure: The study was funded by Boehringer Ingelheim and Eli Lilly.