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Clinical and biochemical characteristics and analysis of risk factors for euglycaemic diabetic ketoacidosis in type 2 diabetic individuals treated with SGLT2 inhibitors: A review of 72 cases over a 4.5-year period.
Menghoum, N, Oriot, P, Hermans, MP
Diabetes & metabolic syndrome. 2021;(6):102275
Abstract
BACKGROUND AND AIMS To study euglycemic diabetic ketoacidosis (euDKA) outcomes associated with sodium-glucose co-transporter 2 inhibitors (SGLT2is) METHODS Review of 72 euDKA cases in T2DM between September 2015 and January 2020 (PUBMED). RESULTS euDKA could occur at any time during SGLT2is treatment, with nausea, abdominal pain and vomiting as main symptoms. Hyperglycemia did not correlate with pH and β-hydroxybutyrates. Low pH and high β-hydroxybutyrates were significantly associated with euDKA. In biguanides users, acidosis was unrelated to lactic acidosis. euDKA occurred during fasting, surgery, acute infection, insulin deprivation (endogenous or exogenous). CONCLUSIONS These data support avoidance of euDKA risk states in SGLT2i users.
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Efficacy of DPP-4 inhibitors and SGLT2 inhibitors compared to sulphonylureas in adult patients with diabetes with low c-peptide levels with or without anti-GAD65 antibody positivity.
Sudan, A, Kalra, A, Mirza, AA, Kant, R
Diabetes & metabolic syndrome. 2021;(4):102197
Abstract
BACKGROUND AND AIMS Latent Autoimmune Diabetes of Adulthood (LADA) is different from type 2 diabetes. Present treatment protocols do not reflect that. DPP-4 and SGLT2 inhibitors have changed therapy. DPP-4 inhibitor use has shown delayed decline in beta-cell reserve in LADA. We studied patients with low c-peptide to assess relationship between c-peptide and anti-GAD65 antibody levels and compare DPP-4 inhibitors with SGLT2 inhibitors and sulphonylureas. METHODS The study was an open-label trial conducted in 156 participants with low c-peptide (<0.8 ng/mL), age > 25 years, recently diagnosed diabetes with HBA1c ≥ 6.5%. Participants were enrolled into three arms: Group A received sulphonylureas + metformin, Group B received DPP-4 inhibitors + metformin, and Group C received SGLT-2 inhibitors + metformin. Serum anti-GAD-65 antibodies were assessed using sandwich ELISA. Participants were assessed on enrolment and after three months of dual pharmacotherapy. RESULTS The three arms were comparable on enrolment. 52% of participants with low c-peptide had high anti-GAD65 antibody titers. Significant differences were observed after three months - DPP-4 inhibitors reduced HbA1c by 1.1 ± 0.3%, compared to SGLT2 inhibitors (0.8 ± 0.13%) and sulphonylureas (0.7 ± 0.3%) CONCLUSION DPP-4 inhibitors appear to provide better glycemic control than alternate therapeutic options in patients with low serum c-peptide.
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Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study.
Kosiborod, M, Berwanger, O, Koch, GG, Martinez, F, Mukhtar, O, Verma, S, Chopra, V, Javaheri, A, Ambery, P, Gasparyan, SB, et al
Diabetes, obesity & metabolism. 2021;(4):886-896
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Abstract
AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.
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Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials.
Singh, AK, Singh, R
Diabetes & metabolic syndrome. 2020;(3):181-187
Abstract
BACKGROUND AND AIMS Type 2 diabetes confers a differential risk of cardiovascular (CV) disease according to the gender. Whether newly approved anti-diabetic drugs like sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that have shown a significant reduction in the CV end-points in CV outcome trials (CVOTs) also have a differential impact gender-wise, is still not clearly known. METHODS We systematically searched the medical database up to December 31, 2019 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs that explicitly reported the outcome of major adverse cardiac events (MACE). Subsequently, we pooled the hazard ratio (HR) of MACE in both sexes separately and meta-analyzed the result gender-wise. RESULTS The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 34,322), demonstrated a significant reduction in MACE in men but not in women (Men - HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.006; Women - HR, 0.88; 95% CI, 0.77 to 1.00; P = 0.06) compared to placebo. The meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 56,004) demonstrated a significant reduction in MACE in both sex (Men - HR, 0.88; 95% CI, 0.82 to 0.93; P < 0.0001; Women - HR, 0.88; 95% CI, 0.79 to 0.99; P = 0.03), against the placebo. CONCLUSIONS The reduction in MACE with SGLT-2Is appears to be significantly less in women with diabetes vs men, while GLP-1RAs confers a similar reduction in MACE, irrespective of the gender. Whether these results are related to inadequate statistical power (underrepresentation of women) in CVOT, or it reflects a true gender difference, still remains to be established.
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Cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in Asians with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials.
Singh, AK, Singh, R
Diabetes & metabolic syndrome. 2020;(4):715-722
Abstract
BACKGROUND AND AIMS Both type 2 diabetes and cardiovascular (CV) disease develops at a younger age in Asians and often have a higher risk of mortality. Both sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown a significant reduction in CV end-points in CV outcome trials (CVOTs). Whether similar CV benefit exists in Asians, is not yet clearly known. METHODS We systematically searched relevant medical database up to January 31, 2020 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs. Subsequently, we meta-analyzed the pooled data of hazard ratio (HR) of major adverse cardiac events (MACE) in Asians. We additionally analyzed the data of heart failure hospitalization (HHF) or CV-death with SGLT-2Is in Asians. RESULTS The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 4987), did not find any significant reduction in MACE (HR, 0.88; 95% CI, 0.67 to 1.15; P = 0.35) and HHF or CV-death (HR, 0.86; 95% CI, 0.55 to 1.36; P = 0.53) in Asians, compared to the placebo. In contrast, the meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 4298) demonstrated a significant reduction in MACE, compared to the placebo (HR, 0.71; 95% CI, 0.59 to 0.86; P < 0.0001). CONCLUSIONS This meta-analysis found a significant reduction in MACE with GLP-1RAs but not with SGLT-2Is in Asians. No significant reduction in HHF or CV-death demonstrated either with SGLT-2Is in Asians. Whether these results are related to an inadequate statistical power, or due to underrepresentation of Asians, or a true ethnic difference, remains to be established.
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Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy.
Cintra, R, Moura, FA, Carvalho, LSF, Barreto, J, Tambascia, M, Pecoits-Filho, R, Sposito, AC
Revista da Associacao Medica Brasileira (1992). 2019;(1):70-86
Abstract
The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.
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Use of flash glucose monitoring system in assessing safety of the SGLT2 inhibitors during Ramadan fasting in high risk insulin treated patients with type 2 diabetes.
Abdelgadir, E, Rashid, F, Bashier, A, Al Saeed, M, Khalifa, A, Alawadi, F, Hassanein, M
Diabetes & metabolic syndrome. 2019;(5):2927-2932
Abstract
BACKGROUND The risks of hypoglycemia, dehydration and kidney injury may theoretically be aggravated by people with type 2 diabetes treated with Insulin and SGLT2 inhibitors during Ramadan. Data on safety and efficacy of SGLT2-I in people with type 2 diabetes treated with insulin is scanty. We aimed to assess the impact of SGLT2 inhibitors during Ramadan in high-risk patients with type 2 diabetes treated with insulin, on hypoglycemia, glycemic control and kidney function. METHODS This is a prospective interventional study on high-risk diabetes patients who insisted on fasting. All patients were treated with insulin ± SGLT2I. All patients received a FGMS and Ramadan focused education. All patients attended clinic before and post Ramadan where they were advised on treatment modification as well as biometric and biochemical measurements. RESULTS 95 patients enrolled in the study and 49 of them were on SGLT2i. There was a no significant change in creatinine in both groups. FGMS showed an improvement in the sensor-calculated HbA1c from 7.3 ± 1.5 to 6.8 ± 1.1 and from 8 ± 1.6 to 7.7 ± 1.5 in the SGLT2 group and the non-SGT2i groups, respectively. The hypoglycemia was predominantly reported during Ramadan between 12:00 to 18:00 h, while in pre-Ramadan readings was during 2400-0600 and 1200-1800 slots. CONCLUSIONS This is the first study that assesses the use of SGLT2i along with insulin during Ramadan, using FGMS in high-risk patients with type 2 diabetes under optimal care. There was minimal interruption of fasting, significant improvement in glycemic control, and no significant change in the kidney function after Ramadan.
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Anthropometric outcomes in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective glycemic control from single center.
Calapkulu, M, Cander, S, Gul, OO, Ersoy, C
Diabetes & metabolic syndrome. 2019;(1):284-288
Abstract
INTRODUCTION Dapagliflozin is an antidiabetic drug that has been used as a member of the new antidiabetic drug group that acts by inhibiting SGLT-2 and increasing urinary glucose excretion. With numerous controlled experimental studies of dapagliflozin, evaluation of real-life data after entry into clinical practice is an important condition. In our study, the effects of dapagliflozin on glycemic control and anthropometric measurements were investigated retrospectively. METHODS A-total of thirty-one type 2 diabetics were enrolled in the study. Data of before dapagliflozin and three and six months of treatment were recorded. RESULTS Dapagliflozin reduced HbA1c levels by 0,9% at 3 months and 0,79% at 6 months. Fasting plasma glucose decreased 41,1 mg/dl in the 3rd and 42 mg/dl in the 6th, postprandiyal glucose decreased 86,3 mg/dl in the 3rd and 74,2 mg/dl in the 6th. In the 3rd and 6th, body weights decreased by 3,3 kg and 4,2 kg, BMI decreased by 1,3 kg/m2 and 1,6 kg/m2 respectively. Similarly, it was observed that the waist circumference decreased by 1,3 cm at the end of 6th. CONCLUSION Our data show that SGLT-2 inhibitors provide glycemic control with reduce HbA1c levels by 0.8-0.9%, and reduce fasting and postprandial plasma glucose levels without increasing the risk of hypoglycemia and causing weight lose around 5% at the six mounths. SGLT-2 inhibitors were found to be more effective in reduce postprandiyal plasma glucose in patients who did not use insulin and fasting plasma glucose in patients with diabetes mellitus less than 10 years.
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Lipid profile in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective lipid profile from single center.
Calapkulu, M, Cander, S, Gul, OO, Ersoy, C
Diabetes & metabolic syndrome. 2019;(2):1031-1034
Abstract
INTRODUCTION Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus which increasing urinary glucose excretion. With numerous controlled experimental studies of dapagliflozin, evaluation of real-life data after entry into clinical practice is an important condition. In our study, the effects of dapagliflozin (10 mg) on lipid profile were investigated retrospectively. METHODS A total of thirty-one type 2 diabetic patients with HbA1c level between 6,5% and 13%, aged 45-80 years and whose body mass index higher than 20 kg/m2 were enrolled to the study. Data before dapagliflozin treatment and three and six months results were recorded. RESULTS Dapagliflozin reduced HbA1c levels by 0,9% at 3 months and 0,79% at 6 months. Total cholesterol level decreased 17,6 mg/dl, LDL cholesterol level decreased 13,4 mg/dl and triglyceride level by 25.9 mg/dl at the 6th months and it is observed that there is no serious side effect on the usage for 6 months. CONCLUSION There are conflicting results about the effect of SGLT2 inhibitors on the lipid profile in the literature. According to our data, dapagliflozin has positive effects on lipid profile as weight and glycemic control and it is well tolerated. Therefore, dapagliflozin therapy is beneficial because of the positive change in lipid profile and weight loss in diabetic patients with overweight and hyperlipidemia.
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Mechanistic effects of SGLT2 inhibition on blood pressure in diabetes.
Yaribeygi, H, Atkin, SL, Sahebkar, A
Diabetes & metabolic syndrome. 2019;(2):1679-1683
Abstract
Diabetes mellitus prevalence is increasing worldwide leading to increased morbidity and mortality through diabetes related microvascular and macrovascular disease. The treatment of hypertension has been shown to be a major therapeutic intervention for the prevention of cardiovascular events and other diabetes related complications in diabetes. Sodium-glucose co-transporter inhibitors (SGLT2i) are newly introduced anti-diabetes drugs that lower blood glucose by the inhibition of glucose reuptake and the induction of glycosuria. However, there is increasing evidence showing their cardiovascular benefit beyond the improvement of glycemic control. Here we review the latest findings on the effect of SGLT2i on blood pressure in diabetes.