Emergence of a New Glucoregulatory Mechanism for Glycemic Control With Dapagliflozin/Exenatide Therapy in Type 2 Diabetes
Authors' conclusion
Our findings provide strong evidence for the emergence of a new long-lasting, glucose-independent, insulin/glucagon-independent, glucoregulatory mechanism via which SGLT2i-induced glycosuria stimulates EGP in patients with T2D. SGLT2i plus GLP-1 receptor agonist combination therapy is accompanied by superior glycemic control vs monotherapy.
Study context
- Population
- Patients with T2D
- Participants
- 75 patients
- Comparison
- Dapagliflozin vs exenatide vs dapagliflozin/exenatide
- Outcome
- Acute study: PG elevation and EGP decrease during OGTT
- Follow-up
- Acute
Methodological details5-hour dual-tracer oral glucose tolerance test (OGTT)
- 5-hour dual-tracer OGTT
Main finding
As reported in the abstract
- Plasma glucose (PG) elevation, EXE
- Δ = 42 ± 1 mg/dL
- PG elevation, dapagliflozin (DAPA)
- Δ = 72 ± 3
- PG elevation, DAPA/EXE (lower than EXE and DAPA)
- Δ = 11 ± 3
- Endogenous glucose production (EGP) decrease, DAPA (lower than EXE)
- Δ = −0.65 ± 0.03 mg/kg/min
- EGP decrease, EXE
- Δ = −0.96 ± 0.07
- EGP decrease, DAPA/EXE (lower than EXE, higher than DAPA)
- Δ = −0.84 ± 0.05
Further findings
PG elevation and EGP decrease during OGTT · 1 month
- PG elevation, EXE
- Δ = 26 ± 1 mg/dL
- PG elevation, DAPA
- Δ = 62 ± 2
- PG elevation, DAPA/EXE
- Δ = 27 ± 1
- EGP decrease, DAPA
- Δ = −0.60 ± 0.05 mg/kg/min
- EGP decrease, EXE
- Δ = −0.77 ± 0.04
- EGP decrease, DAPA/EXE
- Δ = −0.72 ± 0.03
- Similar to acute study
PG elevation and EGP decrease during OGTT · 4 months
- PG elevation, EXE
- Δ = 55 ± 2 mg/dL
- PG elevation, DAPA
- Δ = 65 ± 6
- PG elevation, DAPA/EXE
- Δ = 46 ± 2
- EGP decrease, DAPA (lower than EXE)
- Δ = −0.66 ± 0.04 mg/kg/min
- EGP decrease, EXE
- Δ = −0.84 ± 0.05
- EGP decrease, DAPA/EXE (equal to DAPA, lower than EXE)
- Δ = −0.65 ± 0.03
- Comparable to acute study
Plasma insulin/glucagon
- Changes in plasma insulin/glucagon could not explain higher EGP in DAPA/EXE vs EXE
Original publication
Emergence of a New Glucoregulatory Mechanism for Glycemic Control With Dapagliflozin/Exenatide Therapy in Type 2 Diabetes. J Clin Endocrinol Metab. Published 22 July 2023. doi:10.
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