Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose

Mariam Alatrach, Christina Agyin, Carolina Solis-Herrera, Olga Lavryneko, John Adams, Amalia Gastaldelli, Curtis Triplitt, Ralph A Defronzo, Eugenio Cersosimo

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To examine the effect of SGLT2 inhibitors (SGLT2i) on endogenous glucose production (EGP) in patients with type 2 diabetes after an oral glucose load. RESEARCH DESIGN AND METHODS: Forty-eight patients with type 2 diabetes received an 8-h [3-3H]-glucose infusion (protocol I) to assess EGP response to: 1) dapagliflozin (DAPA), 10 mg; 2) exenatide (EXE), 5 μg s.c.; 3) DAPA/EXE; and 4) placebo (PCB). After 2 weeks (protocol II), patients were restudied with a 5-h double-tracer (i.v. [3-3H]-glucose and oral [1-14C]-glucose) oral glucose tolerance test (OGTT) preceded by PCB, DAPA, EXE, or DAPA/EXE. RESULTS: Protocol I: EGP decreased (P < 0.01) with PCB (2.16 ± 0.15 to 1.57 ± 0.08 mg/kg/min) and EXE (2.13 ± 0.16 to 1.58 ± 0.03) and remained unchanged (P = NS) with DAPA (2.04 ± 0.17 vs. 1.94 ± 0.18) and DAPA/EXE (2.13 ± 0.10 vs. 2.09 ± 0.03). During OGTT, EGP decreased (P < 0.01) with PCB (2.30 ± 0.05 to. 1.45 ± 0.06 mg/kg/min) and EXE (2.53 ± 0.08 to 1.36 ± 0.06); with DAPA (2.20 ± 0.04 vs. 1.71 ± 0.07) and DAPA/EXE (2.48 ± 0.05 vs. 1.64 ± 0.07), the decrease in EGP was attenuated (both P < 0.05). During OGTT, the insulin/glucagon (INS/GCN) ratio increased in PCB (0.26 ± 0.03 vs. 0.71 ± 0.06 μU/mL per pg/mL), whereas in DAPA (0.26 ± 0.02 to 0.50 ± 0.04), the increase was blunted (P < 0.05). In EXE, INS/GCN increased significantly (0.32 ± 0.03 to 1.31 ± 0.08) and was attenuated in DAPA/EXE (0.32 ± 0.03 vs. 0.78 ± 0.08) (P < 0.01). CONCLUSIONS: These findings provide novel evidence that the increase in EGP induced by SGLT2i is present during an oral glucose load. The fact that stimulation of EGP occurs despite elevated plasma insulin and glucagon suggests that additional factors must be involved.

Original languageEnglish (US)
Pages (from-to)1372-1380
Number of pages9
JournalDiabetes care
Volume45
Issue number6
DOIs
StatePublished - Jun 2 2022

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Fingerprint

Dive into the research topics of 'Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose'. Together they form a unique fingerprint.

Cite this