lobeglitazone and Heart-Failure

Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D.. This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone.. From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492).. In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Insulin Resistance; Ischemic Stroke; Logistic Models; Pioglitazone; Secondary Prevention; Stroke; Thiazolidinediones

Thiazolidinedione, an insulin sensitizer, has beneficial effects on glucose metabolism; however, there are concerns regarding weight gain and heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce body weight, increase diuresis, and play a protective role in heart failure. We examined the complementary effects of dapagliflozin, an SGLT2 inhibitor, and lobeglitazone, a thiazolidinedione, in high-fat diet (HFD)-induced obese mice. We treated HFD-induced obese mice with vehicle, dapagliflozin, lobeglitazone, and their combination for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed after 12-week treatment, and body composition was measured by dual-energy X-ray absorptiometry before and after treatment. We analyzed oxygen consumption rate (OCR) using 3T3-L1 cells after treatment of β-hydroxybutyrate and/or lobeglitazone. Treatment with a combination of dapagliflozin and lobeglitazone resulted in a significant decrease in postprandial hyperglycemia compared with dapagliflozin monotherapy, but not compared with lobeglitazone monotherapy. The addition of dapagliflozin to lobeglitazone treatment did not attenuate weight gain compared with lobeglitazone monotherapy in this study. However, this combination prevented the increase of organ weight of liver and heart, and OCR in 3T3-L1 cells was increased after treatment with a combination of β-hydroxybutyrate and lobeglitazone compared to lobeglitazone monotherapy. We confirmed the beneficial effect of lobeglitazone on glucose metabolism; however, we did not find any beneficial effect of dapagliflozin on body weight in HFD-induced obese mice. However, the protective effects of dapagliflozin and lobeglitazone combined therapy on the liver, heart, energy consumption, and β-cell senescence are worth investigating in clinical trials.

Topics: 3-Hydroxybutyric Acid; Animals; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Heart Failure; Hypoglycemic Agents; Insulin; Mice; Mice, Obese; Obesity; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Weight Gain