Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease

Aug 9, 2024Gut

Combined use of SGLT2 inhibitors and metformin linked to liver and other health benefits in type 2 diabetes with fatty liver disease

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Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are associated with a lower risk of liver and non-liver complications in patients with diabetic MASLD compared to other glucose-lowering drugs.

SGLT-2i users had a 24% lower risk of hepatocellular carcinoma (HCC) compared to users of other glucose-lowering drugs.
The risk of liver cirrhosis was reduced by 20% in patients using SGLT-2i.
SGLT-2i users also experienced a 18% lower risk of cardiovascular disease (CVD) and a 34% lower risk of chronic kidney disease (CKD).
Non-liver cancer risk was reduced by 19% in those using SGLT-2i.
A stepwise decreasing risk of complications was observed in users of metformin or SGLT-2i, with the lowest risk in those using both medications.

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OBJECTIVE: Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD.

DESIGN: This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted.

RESULTS: Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76-0.97) and in users of both medications (HRs 0.58-0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61-0.84).

CONCLUSION: In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use.

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Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease

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