Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon
Diabetes Metab J. 2023;47(6):808-817. Published online September 26, 2023
Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.
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Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo Diabetes, Obesity and Metabolism.2024; 26(11): 5065. CrossRef
BACKGROUND Metabolic syndrome (MetS) is constellation of cardiovascular risk factors. There are three typically used definitions of MetS proposed by WHO, IDF and NCEP-ATP III. We conducted this study to compare the associations of MetS by WHO, IDF and NCEP-ATP III definition to various metabolic markers of coronary heart diseases in Korean type 2 diabetes patients. METHODS: We enrolled 151 Korean type 2 diabetes patients in one hospital. Anthropometric and biochemical parameters, including high-sensitivity C-reactive protein (hsCRP), homocysteine, uric acid were measured. And then, we divided MetS group from non-MetS group according to three other definitions. RESULTS: Serum hsCRP level was higher in those with MetS group than non-MetS group by WHO definition (0.33 +/- 0.36 mg/dL vs 0.18 +/- 0.26 mg/dL, P < 0.001). But, there are no difference in MetS group and non-MetS group by IDF and NCEP-ATPIII definition. (By IDF, 0.28 +/- 0.31 mg/dL vs 0.25 +/- 0.34 mg/dL, P = 0.64; By NCEP-ATP III, 0.28 +/- 0.33 mg/dL vs 0.22 +/- 0.32 mg/dL, P = 0.41). Uric acid and homocysteine levels were higher in those with MetS by WHO definition (P < 0.05). Similarly, analyses according to IDF and NCEP ATP III definition showed no significant difference. CONCLUSION: In conclusion, WHO definition of MetS has a stronger relationship with the biochemical markers of coronary heart disease in Korean type 2 diabetes patients.
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Recently type 1 diabetes with acute onset and no evidence of islet autoantibodies have been showed as "fulminant type 1 diabetes" and as novel subtype of type 1B diabetes. The study was made progress in Japan. We report a typical case of fulminant type 1 diabetes. A 24 years old male to be in good condition visited our hospital because of flu-like symptom, diarrhea, and abdominal discomfort. He has no medical history and family history of diabetes. The level of plasma glucose is 962 mg/dL, serum ketone body 5.8 mmol/L, arterial blood pH 7.111 and he was diagnosed as diabetic ketoacidosis. Anti-GAD antibody and islet cell antibody were negative and HbA1c is 5.5%. All of them were compatible with the diagnostic criteria of fulminant type 1 diabetes. After the patient has been treated with insulin, his symptoms were improved and abnormal laboratory data were normalized. We report this case with a review of the literature.
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BACKGROUND High glucose-induced apoptosis has been implicated in the loss of beta-cells of the pancreatic islets in animal models of type 2 diabetes. GLP-1 has been shown to reduce apoptosis by the cAMP-dependent mechanism in beta-cells. Other studies have also shown that elevated levels of intracellular cyclic AMP delayed apoptosis in other types of cells. We investigated whether cAMP-elevating agents could suppress the high glucose-induced apoptosis of isolated rat islets. METHODS: Pancreatic islets were isolated from Sprague-Dawley (SD) rats. The expression of phosphodiesterase (PDE) 3 subtypes was investigated by using extracts of freshly isolated islets and analyzing them by RT-PCR. After 2 days of isolation, the islets were cultured in RPMI-1640 media containing 5% FBS with various glucose concentrations (11.1, 16.7 and 27.8 mM), 5x10-6 M forskolin, 2x10-4 M 3-isobutyl-1-methylxanthine (IBMX), 10-5 M cilostazol, and 10-6, 5x10-6 and 10-5 M H-89 for 5 days. The islet apoptosis was measured by a sandwich enzyme-immunoassay using antihistone antibody. RESULTS: Apoptosis was lowest at 11.1 mM glucose concentration, and increased at higher glucose concentrations (1.00 +/- 0.04 A.U. (arbitrary unit) at 11.1 mM, 1.17 +/- 0.12 A.U. at 16.7 mM, and 1.65 +/-0.13 A.U. at 27.8 mM (P <0.05 for 11.1 mM). Both PDE 3A and 3B mRNA were expressed in the islet extracts. In 16.7 and 27.8 mM glucose concentrations, forskolin (P <0.01), IBMX (P <0.05) and cilostazol (P < 0.05) suppressed apoptosis of the islet cells. Protein kinase A (PKA) nhibitor, H-89, did not prevent the inhibition of apoptosis by forskolin. CONCLUSION: These results show that high glucose-induced apoptosis of the cells in rat islet is attenuated by such cAMP-elevating agents as cilostazol. However, cyclic AMP regulation of islet apoptosis may occur via a PKA-independent signaling pathway.