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Aims: Although it has long been assumed that increased glucagon level participants in the ketosis during sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment, the effect of SGLT2i on glucagon in diabetic patients remains controversial. Hence, we conducted this metanalysis to assess the overall effect of SGLT2i treatment on plasma glucagon level.

Methods: PubMed/MEDLINE, Embase, and Cochrane databases were searched for studies published before August 2020. Clinical trials in type 1 diabetes (T1DM) and type 2 diabetes (T2DM) patients with the report of glucagon variation before and after SGLT2i treatment was included.

Result: In total, 10 trials were included. Overall, SGLT2i treatment was associated with significantly increased fasting plasma glucagon level (WMD, 35.00 pg/ml; 95% CI, 24.48 to 45.52 pg/ml, P<0.01) with significant raise in T1DM and insignificant raise in T2DM (Figure). In T2DM, the use of SGLT2i was associated with elevated fasting glucagon level in the subgroup with more reduction in fasting insulin level (WMD, 13.95 pg/ml; 95% CI, 8.51 to 19.39 pg/ml, P<0.01), but not in the subgroup with less reduction in fasting insulin level.

Conclusions: The increase in fasting glucagon level may be associated with the reduction of insulin, which may decrease the level of insulin-glucagon ratio and make patients susceptible to ketosis.

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Disclosure

X. Zhu: None. C. Lin: None. L. Li: None. S. Hu: None. X. Cai: None. L. Ji: None.

Funding

National Natural Science Foundation of China (81970698, 81970708); Beijing Natural Science Foundation (7202216)

© 2021 by the American Diabetes Association
2021
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