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Body weight influences SGLT2-inhibitor effects in type 1 diabetes


 

REPORTING FROM EASD 2019

DEPICT with dapagliflozin

In a poster, Paresh Dandona, MD, PhD, of the State University of New York at Buffalo, and associates presented data from a pooled analysis of the DEPICT-1 and DEPICT-2 studies looking at safety and efficacy outcomes with dapagliflozin according to five BMI categories: less than or equal to 23 kg/m2; greater than 23 kg/m2 to less than or equal to 25 kg/m2; greater than 25 kg/m2 to less than or equal to 27 kg/m2; greater than 27 kg/m2 to less than or equal to 30 kg/m2; and greater than 30 kg/m2.

The pooled analysis included 548 patients treated with dapagliflozin 5 mg and 532 who received placebo. The investigators found that patients with higher BMIs who were treated with dapagliflozin had greater weight loss, showed a trend toward achieving an HbA1c reduction of 5.5 mmol/mol (greater than or equal to 0.5%) or more without the risk of severe hypoglycemia, and had fewer episodes of definite DKA, compared with those with those with lower BMIs.

The adjusted mean percentage change from baseline in body weight in the lowest BMI (less than or equal to 23 kg/m2) group at week 24 was +0.06 kg for placebo and –2.71 kg for dapagliflozin, and at week 52, +0.33 kg and –2.91 kg, respectively. Corresponding values comparing placebo and dapagliflozin at 24 and 52 weeks in the highest BMI group (greater than 30 kg/m2) were –0.30 kg and –3.03 kg, and +0.56 and –3.58 kg.

Odds ratios for achieving an HbA1c reduction of 5.5 mmol/mol (greater than or equal to 0.5%) without severe hypoglycemia at week 24 with dapagliflozin, compared with placebo, were, in increasing order of BMI groups: 1.85, 1.93, 3.87, 2.91, and 4.20.

“Generally, more events of definite DKA were observed in patients treated with dapagliflozin than in those treated with placebo,” but there were fewer events as BMI increased, Dr. Dandona and associates reported. “These data should be interpreted with caution due to the low number of events in each subgroup,” they added.

The number of adjudicated DKA events comparing dapagliflozin and placebo across the BMI groups were: 4 versus 1 (BMI less than or equal to 23 kg/m2); 6 versus 1 (BMI greater than 23 kg/m2 to less than or equal to 25 kg/m2); 7 versus 1 (BMI greater than 25 kg/m2 to less than or equal to 27 kg/m2); 3 versus 1 (BMI greater than 27 kg/m2 to less than or equal to 30 kg/m2); and 2 versus 1 (BMI greater than 30 kg/m2).

In regard to limitations, “this was a post hoc analysis,” the investigators noted, adding that the studies were not originally powered for comparison between BMI subgroups, so the results should be considered exploratory. Moreover, DKA and hypoglycemia were strictly monitored in the trials, which “may differ from real-world situations,” they said.

The inTandem studies were sponsored by Lexicon and Sanofi. Dr. Danne disclosed receiving research funding and serving as a consultant, advisory board or steering committee member, or speaker for various companies, including Sanofi. Dr. Sawhney is an employee of and holds stoke in Lexicon. The DEPICT studies were sponsored by AstraZeneca. The lead author, Dr. Dandona, disclosed employment or consultancy services for multiple companies, including AstraZeneca.

SOURCE: Danne T et al. EASD 2018, Oral Presentation 2; Dandona P et al. EASD 2019, ePoster 720; Sawhney S et al. EASD 2019, Oral Presentation 3.

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