Reduced Fasting Plasma Glucose Research Articles

Effects of sacubitril/valsartan on both metabolic parameters and insulin resistance in prediabetic non-obese patients with heart failure and reduced ejection fraction.

BackgroundThe effects of sacubitril/valsartan (sac/val) on metabolic parameters and insulin resistance (IR) in non-obese/prediabetic patients have not been previously described.AimTo evaluate the effects of sac/val on glycemic and metabolic parameters, Homeostatic Model Assessment of IR (HOMA-IR), and echocardiographic parameters in prediabetic patients with heart failure with reduced ejection fraction (HFrEF).MethodsFifty-nine patients with HFrEF (EF < 35%) but without obesity and/or type 2 diabetes mellitus have been enrolled. All the patients at baseline and week 24 underwent complete anthropometrical evaluation and were subjected to an echocardiogram test. IR has been assessed by HOMA-IR.ResultsAfter 24-week of treatment with sac/val, a significant reduction in fasting plasma glucose (109 ± 9 vs 103 ± 8 mg/dl, p < 0.0001), fasting plasma insulin (16 ± 4 vs 10 ± 4 UI/L), and hemoglobin A1c (HbA1c) value (6% ± 0.5% vs 5.3% ± 0.3%, p < 0.0001) was observed. Similarly, we observed a significant improvement in IR (HOMA-IR, 4.4 ± 0.9 vs 2.5 ± 0.6, p < 0.0001). The echocardiogram evaluation showed a significant reduction of the left ventricular end-diastolic volume (168 ± 24 vs 158 ± 22 ml, p < 0.05), a significant reduction of the left ventricular end-systolic volume (111 ± 26 vs 98 ± 22 ml, p < 0.005), and a significant reduction of E/e′ ratio. Sac/val use was also associated with an average 5.1% increase in ejection fraction.ConclusionsOur data seem to indicate that sal/val enhances metabolic control and improves insulin resistance also in prediabetic non-obese patients with HFrEF.

Effects of different diets on glycemic control among patients with type 2 diabetes: A literature review.

Background: Globally, type 2 diabetes mellitus (T2DM) is one of the most common diseases, and the incidence is gradually increasing. Diet management could improve the elevated HbA1c levels. Aim: This review aims to examine the effects of different types of diets on glycemic control in patients with T2DM. Methods: PubMed and Google scholar databases were searched. Reports published from the years 1991 to 2021 that focused on the effect of different diets on diabetes control were selected. Results: All the studies reported that the type of diet can affect insulin secretion and glycemic control in patients with diabetes. The recommended macronutrient distribution for patients with diabetes is 30% of fat, 45-60% of carbohydrates, and 15-35% of protein. Consuming more or less of these macronutrients may lead to changes in glucose metabolism and may affect insulin secretion. In fact, following alow-fat diet improves glycemic control and decreases HbA1c levels. Studies reported that a low-carbohydrate diet had the greatest effect on improving glycemic control and insulin parameters. A low-calorie diet reduced fasting plasma glucose, while a very low-calorie diet resulted in a long-term decrease in HbA1c level. A healthy diet free of processed foods and sugar, and rich in nutrients such as fiber, vitamins, and minerals contributed to maintaining controlled blood sugar and lipid plasma levels. Although studies show a low-salt diet improves blood pressure, which is common inT2DM, other findings show that restricting salt intake is associated with increased sugar consumption. Conclusion: Healthy diet with adequate intake of energy and low-fat and low-sugar foods can enhance the glycemic control and reduce T2DM complications.

†Efficacy and Safety of Bempedoic Acid in Patients with Metabolic Syndrome

<h3>Lead Author's Financial Disclosures</h3> MDS has received funding/grant support from Amgen, the National Institutes of Health, and Novartis, and honorarium for consultancy from Amgen, Novartis, Novo Nordisk and Regeneron. <h3>Study Funding</h3> Esperion Therapeutics, Inc. <h3>Background/Synopsis</h3> Metabolic syndrome (MetS) is associated with increased risk of cardiovascular events. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C in patients with hypercholesterolemia. <h3>Objective/Purpose</h3> To assess efficacy and safety of BA in patients with and without metabolic syndrome. <h3>Methods</h3> We investigated the lipid-lowering efficacy, safety, and effect of BA on glycemic parameters and high-sensitivity C-reactive protein (hsCRP) according to baseline metabolic status using pooled data (n=3623) from 4 phase-3, randomized, double-blind studies in which patients were randomized 2:1 to BA or placebo (PBO) for 12-52 weeks. Patients with diabetes mellitus (n=1114) were excluded from the analyses. The remaining patients were categorized as having MetS (n=936; defined using modified IAS guidelines with BMI as a proxy for waist circumference) or nonMetS (n=1573). Assessments included absolute or % change from baseline to week 12 in LDL-C, other lipid parameters, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and hsCRP; and treatment-emergent adverse events (TEAEs). <h3>Results</h3> Background statin intensity was similar between groups (Table). BA significantly lowered LDL C at week 12 vs PBO, to a greater extent in patients with MetS than nonMetS (PBO corrected % change from baseline of −22.3 MetS; −18.4 nonMetS; interaction P=.0472). BA also significantly lowered total cholesterol, non-HDL-C, and apo B % change at week 12 vs PBO to a similar extent in both subgroups. In patients with MetS, absolute reductions in HbA1c and FPG were significantly greater with BA vs PBO; changes in HbA1C and FPG were not significantly different for BA vs PBO in the nonMetS group (interaction P=.0003 and .0017, respectively). hsCRP % change from baseline was substantially lowered with BA vs PBO in both groups (insignificant interaction based on log of hsCRP absolute change). The incidence of TEAEs was comparable in both subgroups.subgroups and greater lowering of LDL-C, HbA1c, and FPG levels in patients with MetS vs nonMetS. <h3>Conclusions</h3> Overall, BA demonstrated comparable safety in both metabolic subgroups and greater lowering of LDL-C, HbA1c, and FPG levels in patients with MetS vs nonMetS.

Efficacy and Safety of Insulin Glargine 300U/mL in People with Type2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

IntroductionThe efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa.MethodsThe ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5–10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed.ResultsA total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (− 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event.ConclusionIn people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions.ClinicalTrials.gov identifierNCT03760991.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01271-7.

339-OR: Oral Small-Molecule GLP-1R Agonist Danuglipron Robustly Reduces Plasma Glucose and Body Weight after Eight Weeks in Japanese Adults with Type 2 Diabetes Mellitus

Danuglipron is an oral small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist shown to reduce plasma glucose and body weight after 28 days of treatment in adults with type 2 diabetes mellitus (T2DM) . This randomized, double-blind (sponsor-open) , placebo-controlled, Phase 1 study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of danuglipron in Japanese patients with T2DM. A total of 37 patients with T2DM inadequately controlled on diet and exercise alone were randomized to twice-daily (BID) oral doses of placebo or multiple, ascending doses of danuglipron titrated to 40 mg, 80 mg, and 120 mg for 8 weeks. Multiple, oral doses of danuglipron were generally safe in Japanese participants with T2DM and resulted in approximate dose-proportional increases in exposure and significant reductions in fasting plasma glucose (FPG) , 24-hour mean daily glucose (MDG) , glycated hemoglobin (HbA1c) , and body weight (Table) . Most adverse events (AEs) were mild or moderate, with AEs of nausea, vomiting, abdominal discomfort, diarrhea, and headache reported most frequently. There were no deaths and no serious AEs related to dosing of danuglipron. No clinically significant adverse trends in labs, electrocardiogram, or vital sign abnormalities were apparent. Disclosure R.Ono: Employee; Pfizer Japan Inc. K.Furihata: Other Relationship; Eli Lilly and Company, Pfizer Japan Inc. Y.Ichikawa: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Japan Inc. Y.Nakazuru: Employee; Pfizer Japan Inc., Stock/Shareholder; Pfizer Inc. A.Bergman: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. D.N.Gorman: Employee; Pfizer Inc. A.R.Saxena: Employee; Pfizer Inc. Funding Sponsored by Pfizer Inc.

181-OR: Sympathetic Activity in Patients with Type 2 Diabetes Mellitus Treated with Empagliflozin or Hydrochlorothiazide

Changes in sympathetic nervous system activity may contribute to beneficial effects of sodium glucose transporter (SGLT2) inhibition on cardiovascular outcomes. We hypothesized that SGLT inhibition with empagliflozin lowers sympathetic activity compared with hydrochlorothiazide (HCT) to discern SGLT2-specific actions from non-specific responses to increased natriuresis. In this double-blind, randomized study patients with type 2 diabetes mellitus on metformin monotherapy received either 25 mg/day empagliflozin (n=20) or 25 mg/day HCT (n=21) for 6 weeks. Muscle sympathetic nerve activity (MSNA) , blood pressure, cardiovascular, and metabolic biomarkers were assessed at baseline and end of treatment. Empagliflozin significantly increased urinary glucose excretion (difference in change from baseline 47.4 mmol/l vs. HCT) , reduced fasting plasma glucose (-1.91 mmol/l) , HbA1c (-0.58%) , and body weight (-1.23 kg, all p&amp;lt;0.05) . Office systolic blood pressure decreased with both treatments. MSNA (burst frequency -1.95 [95% confidence interval -8.67; 4.78] bursts/min) , baroreflex heart rate control (0.84 [-1.18; 2.87] ms/mmHg) and plasma catecholamines did not change significantly with either treatment. MSNA increased with higher body weight loss with both treatments, but more pronounced and significant only with HCT (p=0.0015) . In conclusion, neither empagliflozin nor HCT treatment led to clinically relevant changes in sympathetic activity. Given the important role of the sympathetic nervous system in the progression of cardiovascular disease, mechanisms attenuating sympathetic activity in the face of increased sodium excretion deserve further attention. Disclosure K.Heusser: None. J.Tank: None. A.Fischer: None. T.Heise: Advisory Panel; Novo Nordisk A/S, Research Support; ADOCIA, AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Genova, Nestlé, Neuraly Inc., Novo Nordisk A/S, Sanofi, Zealand Pharma A/S, Speaker's Bureau; Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Novo Nordisk A/S. J.Jordan: Consultant; Novo Nordisk, Other Relationship; Eternygen, Research Support; Boehringer Ingelheim International GmbH.

C77 EFFECT OF SACUBITRIL/VALSARTAN ON BOTH METABOLIC PARAMETER AND INSULIN RESISTANCE IN NON OBESE NON DIABETIC PATIENTS WITH HEART FAILURE

Abstract Background Sacubitril/Valsartan has been shown to improve mortality and reduce hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). Moreover Sacubitril/Valsartan showed a significantly reduction in the HbA1c in diabetic patients. The effect of Sacubitril/Valsartan on metabolic parameter and insulin resistence in both, non obese and non diabetic patients, have not been previously described. Aim We evaluated the effects of the Sacubitril/Valsartan on both glycaemic and metabolic parameter, on HOMA–IR and on echocardiographic parameters in patients with HFrEF. Methods A total of 59 non obese and non diabetic patients with a diagnosis of HFrEF (EF &amp;lt; 35%) have been enrolled. All the patients underwent a complete anthropometrical evaluation, laboratory determinations (including fasting glucose, fasting insulin, HbA1c) and echocardiogram evaluation. Data analysis was made after 24 weeks of treatment. The insulin resistance has been assessed by HOMA–IR. Results Data analysis demostrated a significant reduction in fasting plasma glucose (111.4 + 11.5 vs 106 + 10 mg/dl, P = 0.03), fasting plasma insulin (13.6 + 5.9 vs 10.5 + 4.4 µUI/ml), HbA1c value (6.14 + 0.5% vs 5.9 + 0.3%, P &amp;lt; 0.01) and insulin resistance (HOMA–IR, 3.74 + 2.2 vs 2.7 + 2.1, P = 0.03). The echocardiogram evaluation showed a significant reduction of the end–diastolic left ventricular volume (168 + 44 vs 150 + 38 ml, P &amp;lt; 0.05), a no significant reduction of the end–systolic left ventricular volume (98 + 26 vs 88 + 22 ml, P = 0.07), a significant reduction of E/e1 ratio and an average 7.8% increase in ejection fraction (EF), from a mean baseline of 32.3 + 2.4 to 40.1 + 3.8% (P &amp;lt; 0.0001). No differences in interventricular septal (IVS) thickness, posterior wall (PW) thickness, A–wave, E–wave and E/A ratio have been observed. No differences in anthropometrical parameters (weight, body mass index, waist circumference) and blood pressure were observed. Conclusions Our data, even if preliminary, seem to indicate that sacubitril/valsartan might enhance glycaemic control and improve insulin resistance in non obese/non diabetic patients with HFrEF. Also, our data confirm that sacubitril/valsartan treatment is able to improve ejection fraction in HFrEF patients.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was −1.02% (−1.11, −0.93) in the dorzagliatin group and −0.36% (−0.45, −0.26) in the placebo group (estimated treatment difference, −0.66%; 95% CI: −0.79, −0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile (NCT03141073).

Imeglimin: a new antidiabetic drug with potential future in the treatment of patients with type 2 diabetes.

Imeglimin (IMEG) is the first drug of the "glimin" group. Glimin is a new group of hypoglycaemic drugs for the treatment of patients with type 2 diabetes mellitus (T2DM). The chemical structure and action mechanism of the drug are presented in the paper. Imeglimin is unique and different in action compared to other hypoglycaemic drugs. Imeglimin has been shown to have a beneficial effect on 3 key pathogenetic elements of T2DM, i.e., 1. increased gluconeogenesis, 2. inadequate glucose-induced insulin secretion by beta cells, and 3. peripheral insulin resistance. The peak effect on fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) levels of IMEG is reached after 16 weeks of treatment. Subjects receiving IMEG at 1000- and 1500-mg doses twice daily also achieved significantly greater reductions in fasting plasma glucose (FPG) levels at week 24 compared to the placebo group (IMEG in humans causes increased insulin secretion as well as reductions in fasting plasma glucose and glycated haemoglobin). This paper also presents the pharmacokinetics of IMEG action, clinical evidence for its efficacy, results of phase II and III clinical trials, and drug tolerability. Our paper seems to show that IMEG, with its novel mechanism of action, has a chance to improve treatment results in a larger population of T2DM patients.

Effects of imatinib on glycemic and lipid profiles: a retrospective cohort study

Despite a favorable effect of imatinib on glucose metabolism in animal models, human reports are inconsistent. We retrospectively studied the long-term effect of imatinib on fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), LDL-cholesterol (LDL), and triglycerides (TGs) in a large HMO cohort of patients initiating therapy. In patients with diabetes (n = 118), significant reductions in HbA1c (0.53%, IQR 0.09, 1.19; p < .001) and FPG (10.2 mg/dL, IQR −3.5, 32.2; p < .001), independent of demographics and of glucose-lowering drugs utilization, were observed during the first year of imatinib treatment. Significant reductions in LDL (17.8 mg/dL, IQR −1.3, 34.0; p < .001) and TG (25.0 mg/dL, IQR −2.3, 58.3; p < .001), also independent of demographics and of statin utilization, were evident in the entire cohort (n = 611) during the first imatinib year. All reductions persisted during the second treatment year. To conclude, imatinib is associated with durable metabolic benefits, which may guide TKI choice in patients with cardiovascular co-morbidities.

IDF21-0679 INTENSIFY: effectiveness of insulin degludec/liraglutide (IDegLira) in a real-world T2DM population in the UAE

Background: In patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, combining a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin (BI) offers an effective treatment-intensification strategy. A fixed-ratio combination of insulin degludec and liraglutide (IDegLira; Novo Nordisk) was launched in the United Arab Emirates (UAE) in 2018. Aim: To investigate the effect of IDegLira in a real-world population of patients with T2DM switching from BI or GLP-1 RA (± oral antidiabetic drugs [OADs]) in routine clinical practice in the UAE. Method: INTENSIFY was a 26–38-week, multicentre, prospective, non-interventional, real-world study. T2DM patients (≥18 years) with inadequate glycaemic control on BI or GLP-1 RA (± OADs) were eligible if a switch to IDegLira had been planned. The primary endpoint was change in laboratory measured HbA1c from baseline to end of the study. Secondary endpoints included overall change in fasting plasma glucose (FPG); change in body weight; incidence of hypoglycaemic episodes in the 4-week (non-severe and nocturnal non-severe episodes) and 26-week (severe episodes) periods before end of study (EOS) versus before initiation of IDegLira treatment. Treatment preference and safety were also assessed. ClinicalTrials.gov identifier: NCT03823339 Results: Among 263 patients, 206 (78.3%) and 57 (21.7%) patients had previously received BI ± OADs and GLP-1 RA ± OADs, respectively. Baseline mean HbA1c was 9.29%. Switching to IDegLira was associated with a significant overall reduction in HbA1c, with an estimated mean (SE) change from baseline of –0.9% (0.1%), 95% CI, –1.1 to –0.7 (p<0.0001). There was also a significant reduction in FPG: overall mean (SE) change from baseline was –48.2 (5.9) mg/dL, 95% CI, –59.9 to –36.5 (p<0.0001). A significant reduction in body weight was achieved among patients previously treated with BI ± OADs,with an estimated mean (SE) change from baseline of –1.1 (0.2) kg, 95% CI, –1.5 to –0.6 (p<0.0001). The estimated incidence of hypoglycaemic episodes was numerically lower in the periods before EOS versus before initiation of IDegLira treatment (2 vs. 13, 2 vs. 6, and 2 vs. 4 episodes for non-severe, nocturnal non-severe, and severe hypoglycaemia, respectively). Overall, the number of IDegLira dose steps increased significantly (mean [SE] change, 6.1 [0.6] steps, 95% CI, 5.0–7.2 [p<0.0001]). Most patients (86%) preferred IDegLira over previous treatments. IDegLira was well tolerated with no unexpected safety findings. Discussion: Switching from BI or GLP-1 RA (± OADs) to IDegLira significantly improved glycaemic control in adults with T2DM. There were significant overall reductions in HbA1c and FPG; a significant reduction in body weight among patients previously on BI ± OADs, and a reduction in hypoglycaemic events. Conservative dose titration (an increase of approximately 1 dose step per month) was identified in the INTENSIFY study. A stricter titration schedule and frequent interaction between patients and investigators may have led to greater improvement in both primary and secondary endpoints.

IDF21-0675 IDegAsp treatment was associated with improved glycaemic control and reduced hypoglycaemia rates: a real-world study

Background: Insulin degludec/insulin aspart (IDegAsp) has been shown to provide effective glycaemic control with reduced rates of hypoglycaemia compared with other insulin regimens in a large phase 3 clinical trial programme in people with type 2 diabetes (T2D). Aim: To evaluate glycaemic control and investigate the incidence of hypoglycaemia in people with T2D after initiating or switching to IDegAsp from any anti-diabetic treatment (including oral anti-diabetic drugs [OADs], basal insulin, basal–bolus insulin, premix insulin and glucagon-like peptide-1 receptor agonist [GLP-1 RA] ± insulin) in real-world clinical practice across six countries. Method: This was a 26-week, open-label, non-interventional study (NCT04042441) conducted in Australia, India, Malaysia, Philippines, Saudi Arabia and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp as per local clinical practice. The incidence of self-reported non-severe hypoglycaemic episodes (overall and nocturnal), occurring within 4 weeks prior to IDegAsp initiation (baseline) and 4 weeks prior to end of study (EOS, first visit from week 26–36), and self-reported severe hypoglycaemic episodes, occurring within 26 weeks prior to baseline and 26 weeks prior to EOS, were analysed using a negative binomial regression model. Results: Compared with baseline, there was a significant improvement in HbA1c at EOS (baseline HbA1c [standard deviation], 9.8% [1.99]; estimated change: –1.4% [–1.51;–1.29]95%CI; p < 0.0001 [primary endpoint]). There was also a significant reduction in fasting plasma glucose from baseline to EOS (estimated change: –49.0 mg/dL [–53.77;–44.29]95%CI; p < 0.0001). The overall incidence rates of severe, non-severe and non-severe nocturnal hypoglycaemia decreased significantly between the period prior to baseline and the period before EOS (Table). Discussion: Overall, in a broad, real-world population of adults with T2D, initiating or switching to IDegAsp was associated with improved glycaemic control and significantly lower rates of severe, non-severe and non-severe nocturnal hypoglycaemia.

Efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy for Type 2 Diabetes Mellitus therapy: a meta-analysis.

The aim is to assess the comparative efficacy and safety of combination therapy with vildagliptin and metformin vs. metformin monotherapy in the treatment of type 2 diabetes mellitus (T2DM). We searched on PubMed, Cochrane Library, Web of Science, and Embase databases for randomized controlled trials (RCTs) of combination therapy with vildagliptin and metformin vs. metformin monotherapy in patients with T2DM published up to 30 February 2021. The Cochrane tool and Revman 5.3 software was used to assess the risk of bias and conducted the meta-analysis in the included RCTs. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. A total of 11 RCTs and 8533 patients were included. For the efficacy, we found that combination therapy with vildagliptin and metformin (dose of metformin ≥1500mg/d) had a significantly higher reduction in hemoglobin A1c (HbA1c) [mean differences (MD)= -0.59, 95% CI (-0.28, -0.16), p<0.00001] and fasting plasma glucose (FPG) level [MD= -0.82, 95% CI (-1.09, -0.56), p<0.00001] than combination therapy with vildagliptin and metformin (dose of metformin <1500 mg/d). Vildagliptin plus metformin as combination therapy reduced body weight loss ratio [MD=0.22, 95% CI (0.17, 0.27), p<0.00001] when compared with metformin monotherapy. In terms of safety, the vildagliptin plus metformin as combination therapy did not increase risk of total adverse events (AEs) [RR=0.98, 95% CI (0.94,1.02), p=0.29], however there were significant statistical difference and did not increase the risk of diarrhea [RR=0.55, 95% CI (0.40, 0.76), p=0.0003] and Gastrointestinal (GI) disorders [RR=0.72, 95% CI (0.58, 0.91), p=0.006], but significantly increased risk of dizziness [RR=1.41, 95% CI (1.06, 1.88), p=0.02] when compared with metformin monotherapy. Compared with metformin, vildagliptin combined with metformin could significantly reduce FPG, HbA1c and body weight. When the dose of metformin in the combination group of vildagliptin and metformin is ≥1500mg/d, the results showed significant reduction in HbA1c and FPG. In addition, it had no risk of increase in total AEs, diarrhea, and GI disorders, but had significant risk of increase in dizziness. GRADE showed that the quality of evidence had high certainty in FPG and moderate certainty in HbA1c, body weight and all AEs.

Improvement of glycemic indices by a hypocaloric legume-based DASH diet in adults with type 2 diabetes: a randomized controlled trial.

The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors. This study was a randomized controlled trial. Three-hundred participants, aged 30-65years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets. A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoproteincholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters. The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele. Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17).

Is calorie restriction beneficial for normal-weight individuals? A narrative review of the effects of weight loss in the presence and absence of obesity.

Calorie restriction regimens are popular for their purported health-promoting effects. However, it is unclear whether chronic reduction in energy intake and subsequent weight loss have beneficial effects in the absence of obesity. To this end, the results of studies that examined the effects of the same diet-induced weight loss in individuals with and without obesity were reviewed. The contribution of lean mass to the total amount of weight lost is greater in participants without obesity than in those with obesity, but the reductions in resting, nonresting, and total energy expenditure are of similar magnitude. Both in the presence as well as in the absence of obesity, weight loss decreases visceral adipose tissue and liver fat, increases insulin sensitivity in skeletal muscle (insulin-mediated whole-body glucose disposal rate) and in adipose tissue (meal-induced or insulin-induced suppression of plasma free fatty acid concentration), and augments insulin clearance rate, without affecting pancreatic insulin secretion. These effects are of similar magnitude in participants with and without obesity and result in reductions in fasting plasma glucose and insulin concentrations. These data suggest that the same degree of calorie restriction and the same amount of weight loss have multiple beneficial effects on health outcomes in individuals without obesity, similar to those observed in individuals with obesity.

The SGLT2 inhibitor dapagliflozin promotes systemic FFA mobilization, enhances hepatic β-oxidation, and induces ketosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to increase ketone bodies in patients with type 2 diabetes; however, the underlying mechanisms have not been fully elucidated. Here we examined the effect of the SGLT2 inhibitor dapagliflozin (1 mg/kg/day, formulated in a water, PEG400, ethanol, propylene glycol solution, 4 weeks) on lipid metabolism in obese Zucker rats. Fasting FFA metabolism was assessed in the anesthetized state using a [9,10-3H(N)]-palmitic acid tracer by estimating rates of plasma FFA appearance (Ra), whole-body FFA oxidation (Rox), and nonoxidative disposal (Rst). In the liver, clearance (Kβ-ox) and flux (Rβ-ox) of FFA into β-oxidation were estimated using [9,10-3H]-(R)-bromopalmitate/[U-14C]palmitate tracers. As expected, dapagliflozin induced glycosuria and a robust antidiabetic effect; treatment reduced fasting plasma glucose and insulin, lowered glycated hemoglobin, and increased pancreatic insulin content compared with vehicle controls. Dapagliflozin also increased plasma FFA, Ra, Rox, and Rst with enhanced channeling toward oxidation versus storage. In the liver, there was also enhanced channeling of FFA to β-oxidation, with increased Kβ-ox, Rβ-ox and tissue acetyl-CoA, compared with controls. Finally, dapagliflozin increased hepatic HMG-CoA and plasma β-hydroxybutyrate, consistent with a specific enhancement of ketogenesis. Since ketogenesis has not been directly measured, we cannot exclude an additional contribution of impaired ketone body clearance to the ketosis. In conclusion, this study provides evidence that the dapagliflozin-induced increase in plasma ketone bodies is driven by the combined action of FFA mobilization from adipose tissue and diversion of hepatic FFA toward β-oxidation.

Teneligliptin versus vildagliptin in Indian patients with type 2 diabetes inadequately controlled with metformin

India is heading towards being the diabetes capital of the world indicating that every fifth diabetic in the world is an Indian. The aim to prevent and control diabetic complications can be achieved with a target of glycated haemoglobin (HbA1c) less than 7.0%. There is an urgent need for a cost-effective and safer therapeutic approach for the management of type 2 diabetes. The primary objective was to compare the reduction in fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-h PPG), and HbA1c, in Group-1and Group-2 at 6, 12, 18 and, 24 weeks with baseline values of two groups. This was a 24-week, randomized, open-label study. Patients with type 2 diabetes who were inadequately controlled on Metformin (850mg, twice a day) were randomized into two groups, Group-1(Metformin 850mg, twice daily added with Vildagliptin 50mg, twice daily) and Group 2(Metformin 850mg, twice daily added with Teneligliptin 20mg, once a day). Reductions in fasting plasma glucose, 2 hours postprandial plasma and HbA1c in the vildagliptin group (Group1) were comparable with the teneligliptin group (Group2). Patients in both groups showed similar tolerability with lesser episodes of hypoglycemia and, are weight neutral. Teneligliptin is noninferior to vildagliptin in controlling glycaemic parameters and shows similar tolerability.

Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice.

PurposeThis study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.Materials and MethodsThe study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment.ResultsThe baseline HbA1c was 8.3±1.3% (8.7±1.5% in the add-on group and 8.1±1.0% in the switch group). After 12 months, mean HbA1c decreased (-0.91%) in all patients (p<0.05) (-1.39% in the add-on group and -0.63% in the switch group). Significant reductions in FPG were also observed in both the add-on and switch groups (-54.37 mg/dL and -24.68 mg/dL, respectively). Overall, there was a significant improvement in serum triglyceride (-24.74 mg/dL), low density lipoprotein cholesterol (-7.92 mg/dL), body weight (-2.98 kg), VFA (-9.00 cm2), and systolic blood pressure (-8.67 mm Hg). Approximately 35.8% of patients achieved HbA1c <7.0% after 12 months.ConclusionDapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Magnesium supplementation for glycemic status in women with gestational diabetes: a systematic review and meta-analysis

Objective The effect of magnesium supplementation on glycemic status in women with gestational diabetes remains controversial and this meta-analysis aims to explore the efficacy of magnesium supplementation for gestational diabetes. Methods We have searched PubMed, Excerpta Medica database, Web of science, Elton B. Stephens. Company, and Cochrane library databases. The meta-analysis included randomized controlled trials (RCTs) assessing the effect of magnesium supplementation for gestational diabetes and was performed using the random-effect model. Results Four RCTs were included in the meta-analysis. Overall, compared with placebo in gestational diabetes, magnesium supplementation was associated with significantly reduced fasting plasma glucose (standard mean difference [SMD] = −0.99; 95% confidence interval [CI] = −1.28 to −0.70; p < .00001), serum insulin (SMD = −0.75; 95% CI = −1.24 to −0.26; p = .003), homeostasis model assessment of insulin resistance (SMD = −0.74; 95% CI = −1.10 to −0.39; p < .0001) and increased quantitative insulin sensitivity check index (SMD = 0.47; 95% CI = 0.12 to 0.82; p = .008). In addition, low-density lipoprotein-cholesterol (SMD = −0.39; 95% CI = −0.73 to −0.04; p = .03) and total cholesterol (SMD = −0.62; 95% CI = −0.97 to −0.27; p = .0005) were also obviously decreased in the magnesium group than those in the control group. Conclusion Magnesium supplementation benefits glycemic control for gestational diabetes.

Abstract 9797: Efficacy and Safety of Bempedoic Acid in Patients with Metabolic Syndrome

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular events. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C in patients with hypercholesterolemia. We investigated the lipid-lowering efficacy, safety, and effect of BA on glycemic parameters and high-sensitivity C-reactive protein (hsCRP) according to baseline metabolic status using pooled data (n=3623) from 4 phase 3, randomized, double-blind studies in which patients were randomized 2:1 to BA or placebo (PBO) for 12-52 weeks. Patients with diabetes mellitus (n=1114) were excluded from the analyses. The remaining patients were categorized as having MetS (n=936; defined using modified IAS guidelines with BMI as a proxy for waist circumference) or nonMetS (n=1573). Assessments included absolute or % change from baseline to week 12 in LDL-C, other lipid parameters, hemoglobin A 1c (HbA 1c ), fasting plasma glucose (FPG), and hsCRP; and treatment-emergent adverse events (TEAEs). Background statin intensity was similar between groups (Table). BA significantly lowered LDL-C at week 12 vs PBO, to a greater extent in patients with MetS than nonMetS (PBO-corrected % change from baseline of –22.3 MetS; –18.4 nonMetS; interaction P =.0472). BA also significantly lowered total cholesterol, non-HDL-C, and apo B % change at week 12 vs PBO to a similar extent in both subgroups. In patients with MetS, absolute reductions in HbA 1c and FPG were significantly greater with BA vs PBO; changes in HbA 1C and FPG were not significantly different for BA vs PBO in the nonMetS group (interaction P =.0003 and .0017, respectively). hsCRP % change from baseline was substantially lowered with BA vs PBO in both groups (insignificant interaction based on log of hsCRP absolute change). The incidence of TEAEs was comparable in both subgroups. Overall, BA demonstrated comparable safety in both metabolic subgroups and greater lowering of LDL-C, HbA 1c , and FPG levels in patients with MetS vs nonMetS.