Abstract
AimsTo explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes.Materials and methodsIn this single‐centre, double‐blind trial, we randomized 50 obese adults without diabetes (aged 18–70 years; body mass index 30–45 kg/m2) to oral dapagliflozin 10 mg once daily plus subcutaneous long‐acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately.ResultsOf 25 dapagliflozin/exenatide‐ and 25 placebo‐treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was −4.13 kg (95% confidence interval −6.44, −1.81; P < .001), which was mostly attributable to adipose tissue reduction without lean tissue change; 36.0% versus 4.2% of participants achieved ≥5% body weight loss, respectively; and prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P < .01). The difference in SBP change for dapagliflozin/exenatide versus placebo was −6.7 mm Hg. As expected, nausea and injection‐site reactions were more frequent with dapagliflozin/exenatide than with placebo. Only two and three participants, respectively, discontinued because of adverse events.ConclusionsCompared with placebo, dapagliflozin/exenatide dual therapy reduced body weight, frequency of prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes.
Highlights
More than 1.9 billion adults were overweight [body mass index (BMI) ≥25 kg/m2] in 2014, and of these, 600 million were obese (BMI ≥30 kg/m2).[1]
Investigator-sponsored, 24-week, single-centre, randomized, parallel-group, double-blind, placebo-controlled phase IIa study (Figure 1A), we evaluated the efficacy and safety of dual therapy with dapagliflozin 10 mg once daily and exenatide 2 mg once weekly in obese participants without diabetes (ClinicalTrials.gov identifier: NCT02313220)
Classes of glucose-lowering agents for type 2 diabetes (T2D) treatment that reduce body weight include sodium-glucose co-transporter-2 (SGLT2) inhibitors and GLP-1RAs. These two drug classes have rarely been evaluated together in T2D trials and their dual effects on body weight loss have not been previously studied in obese adults without diabetes
Summary
More than 1.9 billion adults were overweight [body mass index (BMI) ≥25 kg/m2] in 2014, and of these, 600 million were obese (BMI ≥30 kg/m2).[1]. Combination therapy with agents acting via different mechanisms may be the most effective pharmacological approach to treating obesity and addressing evolutionary counter-regulatory mechanisms that maintain body weight.[25] For example, calorie loss through increased urinary glucose excretion with SGLT2 inhibitor treatment may lead to increased appetite,[8] which might be countered by a GLP1RA. Combining these treatments seems appropriate to enhance and sustain body weight loss. To the best of our knowledge, this is the first report of a randomized controlled trial evaluating initiation of dual therapy with an SGLT2 inhibitor and a GLP1-RA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
