Hormone‐substrate changes with exenatide plus dapagliflozin versus each drug alone: The randomized, active‐controlled DURATION‐8 study

Aim To determine the effects of individual and combined therapies on plasma insulin, glucagon, β‐hydroxybutyrate (β‐OH) and associated metabolites. Materials and Methods In DURATION‐8, the combination of once‐weekly exenatide (EQW) + 10 mg dapagliflozin (Dapa) in patients with type 2 diabetes poorly...

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Published in:Diabetes, obesity & metabolism obesity & metabolism, 2020-01, Vol.22 (1), p.99-106
Main Authors: Ferrannini, Ele, Baldi, Simona, Frías, Juan P., Guja, Cristian, Hardy, Elise, Repetto, Enrico, Jabbour, Serge A., DeFronzo, Ralph A.
Format: Article
Language:English
Subjects:
Antidiabetics
Benzhydryl Compounds - administration & dosage
Benzhydryl Compounds - therapeutic use
Blood Glucose
Body weight
combination therapy
Creatinine
dapagliflozin
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Diabetic ketoacidosis
Drug Therapy, Combination
exenatide
Exenatide - administration & dosage
Exenatide - therapeutic use
Fasting
Fatty acids
Glucagon
glucagon‐like peptide‐1 agonist
Glucosides - administration & dosage
Glucosides - therapeutic use
glycaemic control
Glycerol
Hematocrit
Humans
Hypoglycemic Agents - therapeutic use
Insulin
Ketoacidosis
Metabolites
Metformin
sodium‐glucose co‐transporter‐2 inhibitor
Urine
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Summary:Aim To determine the effects of individual and combined therapies on plasma insulin, glucagon, β‐hydroxybutyrate (β‐OH) and associated metabolites. Materials and Methods In DURATION‐8, the combination of once‐weekly exenatide (EQW) + 10 mg dapagliflozin (Dapa) in patients with type 2 diabetes poorly controlled with metformin‐reduced HbA1c levels and body weight (at weeks 28 and 52) was compared with EQW + placebo (Plb) or Dapa + Plb. The study included 678 patients randomized 1:1:1 to EQW + Dapa, EQW + Plb, or Dapa + Plb. Plasma insulin and glucagon were measured at fasting and 2 hours after a mixed meal. Fasting plasma free fatty acids (FFA) and β‐OH concentrations were measured. Results The fasting insulin‐to‐glucagon molar ratio (I/Glg) increased with EQW + Plb only; postprandial I/Glg increased in all groups but significantly more with EQW + Plb. β‐OH, FFA, and glycerol concentrations showed a parallel response: larger increments with Dapa + Plb, larger decrements with EQW + Plb, and intermediate changes with EQW + Dapa. β‐OH levels and I/Glg were inversely related to one another. Patients in the top quartile of β‐OH changes from baseline [median (interquartile range): +207 (305) vs. −65 (−154) μmol/L; P 
ISSN:1462-8902
1463-1326
DOI:10.1111/dom.13870