Reduced Fasting Plasma Glucose Research Articles

Short-term effects of obesity surgery versus low-energydiet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI.

Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes. In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic-euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change. One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: -7.7±1.4 kg and -7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (-26.3% [95% CI -49.5, -3.0], p=0.009) and non-significantly following LCD (-20.9% [95% CI -58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected. The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks. ClinicalTrials.gov NCT02988011 FUNDING: This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union's Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants.

Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.

This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.

Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κβ, and Upregulating Nrf2.

Potent hypoglycemic and antioxidant effects were recently reported for the apple-derived phenolic compound phloretamide (PLTM). The renoprotective effects of this compound are yet to be shown. This study aimed to examine the potential of PLTM to prevent diabetic nephropathy in streptozotocin-induced diabetic rats and to examine the possible mechanisms of protection. Non-diabetic and STZ-diabetic male rats were treated orally by gavage with either the vehicle or with PTLM (200 mg/kg; twice/week) for 12 weeks. PTLM significantly increased urine volume and prevented glomerular and tubular damage and vacuolization in STZ-diabetic rats. It also increased creatinine excretion and reduced urinary albumin levels and the renal levels of kidney injury molecule-1 (KIM-1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), neutrophil gelatinase-associated lipocalin (NGAL), and nephrin in the diabetic rats. PTLM also prevented an increase in the nuclear levels of NF-κβ, as well as the total levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), caspase-3, and Bax in the kidneys of diabetic rats. These effects were associated with reduced serum levels of triglycerides, cholesterol, and low-density lipoprotein cholesterol. In both the control and diabetic rats, PTLM significantly reduced fasting plasma glucose and enhanced the renal mRNA and cytoplasmic levels of Nrf2, as well as the levels of Bcl2, superoxide dismutase (SOD), and glutathione (GSH). However, PTLM failed to alter the cytoplasmic levels of keap1 in diabetic rats. In conclusion, PTLM prevents renal damage and dysfunction in STZ-diabetic rats through its hypoglycemic and hypolipidemic activities, as well as through its antioxidant potential, which is mediated by activating the Nrf2/antioxidant axis.

Impact of insulin sensitization on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity-A systematic review, meta-analysis, and meta-regression.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. This systematic review, meta-analysis, and meta-regression aims to compare the effect of insulin sensitizer pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov, and EudraCT for trials published from inception to November 13, 2023. Inclusion criteria were double-blind, randomized controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitization pharmacotherapy versus placebo or other agents. The primary outcomes were changes from baseline BMI, fasting blood glucose, and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitizer pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA-IR, sex hormone binding globulin, and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitizers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitizers' effects on objective measures of fecundity.

Leaf extracts of Euclea natalensis A.D.C ameliorate biochemical abnormalities in high-fat-low streptozotocin-induced diabetic rats through modulation of the AMPK-GLUT4 pathway

ABSTRACT Euclea natalensis is a commonly used plant in traditional African medicine for treating several diseases, including diabetes. The objective of the present study was to evaluate the antidiabetic effects of the leaf extracts of Euclea natalensis and elucidate some of its mechanisms of action. High-fat diet – low Streptozotocin-induced diabetic Sprague Dawley rats were orally treated with the methanol and dichloromethane extracts (100 and 200 mg/kg bw), and their fasting blood glucose levels, body weights, and food and water intake were measured every seven days for 21 days. Biomarkers of oxidative stress, lipid profile, gluconeogenic enzyme activities, glucose transporter 4 (GLUT 4) protein expression, and AMP-activated protein kinase (AMPK) gene expression were also determined. The 200 mg/kg bw of methanol extracts significantly reduced fasting plasma glucose, glycated hemoglobin (HbAc1), triglycerides, and low-density lipoprotein levels. The extract increased insulin sensitivity and hepatic glycogen synthesis, decreased hepatic glucose output, and increased the activities of antioxidant enzymes in diabetic animals after 21 days of treatment. The methanol extract also significantly upregulated the relative expression of GLUT 4 protein via the promoted expression of skeletal muscle and hepatic AMPK. Histological investigation showed ameliorated pancreatic degeneration and expedited regeneration of islets of Langerhans in diabetic rats treated with the methanol extract compared with the dichloromethane extract. The findings demonstrated that Euclea natalensis has beneficial effects on the biochemical and cell abnormalities of type 2 diabetes, partly via the modulation of the AMPK – GLUT 4 pathway.

The effectiveness of pharmacological and lifestyle interventions to reduce the risk of diabetes and hyperglycaemia following gestational diabetes: A systematic review and meta-analysis.

To synthesize the available evidence to better understand the effectiveness of interventions to prevent or delay hyperglycaemia and Type 2 diabetes mellitus (T2DM) postnatally in women with current or previous gestational diabetes mellitus (GDM). We searched five databases up to December 2020 for primary peer-reviewed articles reporting postpartum glycaemic outcomes in women with (previous) GDM following pharmacological or lifestyle intervention. Outcomes were relative risk of T2DM or continuous measures of glycaemia, change or at follow-up. A minimum of two studies evaluating the same intervention-outcome combination were needed to conduct meta-analyses, otherwise studies were described narratively. Meta-regression was used to evaluate whether associations varied by additional variables. We assessed risk of bias using the Critical Appraisal Skills Programme checklist. PROSPERO record CRD42018102380. We included 31 studies in the review with a total sample size of 8624 participants, and 26 studies in meta-analyses. Two-thirds of studies followed up participants at 1 year or less. Pharmacological interventions were associated with reduced risk of T2DM (0.80 [95% CI 0.64-1.00], n = 6 studies), as were lifestyle interventions albeit with a smaller effect size (0.88 [95% CI 0.76-1.01], n = 12 studies). Dietary and physical activity interventions were associated with a small reduction in fasting plasma glucose, particularly in longer interventions, but inconsistent effects were seen for other continuous outcomes. Although possibly due to chance, interventions to reduce hyperglycaemia after GDM may be effective. Future research should improve understanding of how interventions affect glucose control and how to optimise interventions for this population.

Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300Units/mL in Insulin-Naïve Korean People with Type2 Diabetes: TOBE Study.

The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300units/mL (Gla-300) in insulin-naïve Korean people with type2 diabetes mellitus (T2DM) in a real-world setting. This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24weeks. Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4years, P = 0.0378). This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.

Effectiveness and safety of the combination of sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.

Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting. Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively. The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (- 1.71 [- 2.74, - 0.67]; p = 0.001), SBP (- 6.35 [- 10.17, - 2.53]; p = 0.001), HbA1c levels (- 1.48 [- 1.75, - 1.21]; p < 0.00001), and FPG (- 2.27 [- 2.78, - 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant. This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to-action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.

Effect of dapagliflozin on blood glucose control, cardiac function, and myocardial injury markers in patients with type 2 diabetes and heart failure

Purpose: To investigate the impact of dapagliflozin treatment on blood glucose control, cardiac function, and myocardial injury markers in patients with type 2 diabetes and heart failure. &#x0D; Methods: In a retrospective analysis of clinical data for 132 patients with type 2 diabetes and heart failure admitted to Beijing Tongren Hospital, China from January 2020 to June 2021, these patients were stratified into two groups (66 patients each). Control group received conventional pharmacotherapy and study group received additional treatment with dapagliflozin. Both treatment courses lasted for 6 months. The levels of blood glucose control, cardiac function, and myocardial injury markers before and after 6 months of treatment were compared between the two groups, as well as safety during treatment. &#x0D; Results: After 6 months of treatment, both groups exhibited significant reductions in fasting plasma glucose (FPG), 2-h postprandial glucose (2 h PG), glycated hemoglobin (HbA1c), N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), creatine kinase-MB isoenzyme activity (CK-MB), aspartate aminotransferase (AST) levels, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, with study group showing a greater improvement (p &lt; 0.05). &#x0D; Conclusion: Dapagliflozin enhances blood glucose control and cardiac function, improving quality of life in patients with type 2 diabetes and heart failure. Furthermore, Dapagliflozin demonstrates a safe and well-tolerated profile. Future studies will require establishing the mechanism of dapagliflozin action in a larger and more diverse population.

Evaluation of Efficacy and Safety of Empagliflozin in Bangladeshi Patients with Type 2 Diabetes Mellitus (EFFISAEM Study)

Abstract Background: Empagliflozin is a relatively newer glucose-lowering drug (GLD) with many extra-glycemic benefits. To date, no study has evaluated the efficacy and safety of empagliflozin in Bangladeshi patients with type 2 diabetes mellitus (T2DM). Objectives: To assess the efficacy and safety of empagliflozin as an add-on to ongoing GLDs in Bangladeshi adults with uncontrolled T2DM. Materials and Methods: This real-world, multicenter, open-label, prospective study was carried out at 21 sites throughout Bangladesh from 1 February 2022 to 31 July 2022. Patients with T2DM who met the criteria had Empagliflozin added to their existing GLD treatment, with necessary modifications to their ongoing medication regimen. The efficacy and safety data were collected 12 weeks after empagliflozin initiation. Results: Out of 1449 subjects initiating empagliflozin, 1340 subjects [age 50.3 ± 9.0 years, male 52.5%, overweight/obese 94.4%, insulin-treated 25.7%, baseline hemoglobin A1c (Hba1c) 9.9 ± 1.4%] completed the study. At 12 weeks, the reduction in HbA1c was 1.6% (95% CI 1.5-1.6, P &lt; 0.001); 12.5% of the study subjects achieved HbA1c &lt; 7%. There were also significant (P &lt; 0.001 in all instances) reductions in fasting plasma glucose (3.0 mmol/L), plasma glucose 2 hours after breakfast (4.8 mmoL/L), body weight (1.9 kg), body mass index (0.8 kg/m2), systolic blood pressure (BP) (10 mmHg), diastolic BP (7 mmHg), insulin dose (3 U), serum creatinine (0.06 mg/dL), total cholesterol (18 mg/dL), low-density lipoprotein cholesterol (13 mg/dL), high-density lipoprotein cholesterol (1 mg/dL), and triglyceride (42 mg/dL) and an increase in estimated glomerular filtration rate (4.2 mL/min/1.73 m2) from the baseline values. 6.62% experienced adverse events (lightheadedness 2.21%, genital tract infection 0.97%, urinary tract infection 1.24%, generalized weakness 0.48%, and nocturia 0.48%). 1.1% of subjects experienced hypoglycemia, and other 0.12% reported severe hypoglycemic events. Conclusion: Empagliflozin is effective, safe, and tolerable for treating Bangladeshi patients with uncontrolled T2DM as add-on therapy in routine clinical practice with favorable effects on body weight, BP, lipid profile, and renal function.

Single Center Evaluation of Long-Term Results of Glargin U-300 in Insulin Naive Patients In a Real-World Setting

Objective: Insulin therapy stands as one of the most effective and well-established therapeutic options for managing glycemic control in Diabetes Mellitus (DM). Glargine 300 U/mL (Gla-300) represents a new long-acting insulin analog, which has demonstrated a decrease in the risk of hypoglycemia and a reduction in the total number of injections due to prolonged insulin absorption. In this study, we investigated the long-term effects of Gla-300 on Fasting Plasma Glucose (FPG) and HbA1c levels, as well as the incidence of hypoglycemia in insulin-naive patients admitted to the Internal Medicine outpatient clinic, over a period of 0, 3, 6, 12, and 24 months.. Material and Methods: Between January 2018 and June 2022, insulin-naive patients diagnosed with Type 2 Diabetes Mellitus (T2DM) who initiated treatment with Gla-300 and sought care at the Internal Medicine outpatient clinic were subjected to retrospective analysis. Results: The study included 49 insulin-naive patients. A statistically significant decrease was observed in Fasting Plasma Glucose (FPG) (p = 0.03) and HbA1c (p = 0.02) levels during the 24-month follow-up period of Glargine U-300. Additionally, a significant reduction in both FPG (p &lt; 0.01) and HbA1c (p &lt; 0.01) values was achieved at the time of diagnosis and at 3 months. Hypoglycemia was reported in only 1 patient (2%) during our study, indicating a very low hypoglycemia rate. Conclusion: Diabetes mellitus (DM) poses a significant public health challenge, resulting in economic burden and diminished quality of life. Developed to address these challenges, Gla-300 serves as a long-acting basal insulin that effectively reduces the risk of hypoglycemia while offering targeted glycemic control, as evidenced by our study findings. In Turkey, there is a pressing need for multicenter, prospective real-world studies that incorporate parameters such as insulin dosage and weight monitoring.

Assessment of the impact of a personalised nutrition intervention in impaired glucose regulation over 26 weeks: a randomised controlled trial

Dietary interventions can reduce progression to type 2 diabetes mellitus (T2DM) in people with non-diabetic hyperglycaemia. In this study we aimed to determine the impact of a DNA-personalised nutrition intervention in people with non-diabetic hyperglycaemia over 26 weeks. ASPIRE-DNA was a pilot study. Participants were randomised into three arms to receive either (i) Control arm: standard care (NICE guidelines) (n = 51), (ii) Intervention arm: DNA-personalised dietary advice (n = 50), or (iii) Exploratory arm: DNA-personalised dietary advice via a self-guided app and wearable device (n = 46). The primary outcome was the difference in fasting plasma glucose (FPG) between the Control and Intervention arms after 6 weeks. 180 people were recruited, of whom 148 people were randomised, mean age of 59 years (SD = 11), 69% of whom were female. There was no significant difference in the FPG change between the Control and Intervention arms at 6 weeks (− 0.13 mmol/L (95% CI [− 0.37, 0.11]), p = 0.29), however, we found that a DNA-personalised dietary intervention led to a significant reduction of FPG at 26 weeks in the Intervention arm when compared to standard care (− 0.019 (SD = 0.008), p = 0.01), as did the Exploratory arm (− 0.021 (SD = 0.008), p = 0.006). HbA1c at 26 weeks was significantly reduced in the Intervention arm when compared to standard care (− 0.038 (SD = 0.018), p = 0.04). There was some evidence suggesting prevention of progression to T2DM across the groups that received a DNA-based intervention (p = 0.06). Personalisation of dietary advice based on DNA did not result in glucose changes within the first 6 weeks but was associated with significant reduction of FPG and HbA1c at 26 weeks when compared to standard care. The DNA-based diet was effective regardless of intervention type, though results should be interpreted with caution due to the low sample size. These findings suggest that DNA-based dietary guidance is an effective intervention compared to standard care, but there is still a minimum timeframe of adherence to the intervention before changes in clinical outcomes become apparent.Trial Registration:www.clinicaltrials.gov.uk Ref: NCT03702465.

Ipragliflozin and sitagliptin differentially affect lipid and apolipoprotein profiles in type 2 diabetes: the SUCRE study

BackgroundSGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters.MethodsThis is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20–74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120–399 mg/dL (1.35–4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment.ResultsIpragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin.ConclusionsWhile ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.

Efficacy and safety of insulin glargine 300 units/mL vs insulin degludec in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Ultra-long-acting insulin analogs [insulin degludec (IDeg) and insulin glargine 300 units/mL (IGla-300)] offer a longer duration of action with less risk of hypoglycemia compared to other long-acting insulins. However, data about the comparative efficacy and safety are inconsistent. We searched CENTRAL, PubMed, Embase, ICTRP Search Portal, and ClinicalTrials.gov on 7 October 2022. Randomized controlled trials (RCTs) comparing the safety and efficacy of IDeg (100 or 200 units/mL) and IGla-300 in patients with type 1 or type 2 diabetes were included. Three review authors independently selected trials, assessed the risk of bias, extracted data, and evaluated the overall certainty of the evidence using GRADE. The primary outcomes were the change in glycated hemoglobin (HbA1c) and any hypoglycemia; the secondary outcomes were the change in fasting plasma glucose (FPG) and severe and nocturnal hypoglycemia. Four open-label RCTs were included (2727 participants), 3 parallel and 1 cross-over. Overall, the risk of bias assessment yielded some concern or high risk. There was a comparable change in HbA1c from baseline to the end of treatment, a mean difference of 0.07% (95% confidence interval (CI) 0.06 - 0.19; p = 0.29; 3 trials; 2652 patients; very low-certainty evidence), and a comparable rate of any hypoglycemia, rate ratio 1.02 (95% CI 0.8 - 1.3; p = 0.87; 3 trials; 2881 patients; very low-certainty evidence). IDeg resulted in more reduction in FPG compared to IGla-300, mean difference of 10.27 mg/dL (95% CI 7.25 - 13.29; p < 0.001; 3 trials; 2668 patients; low-certainty evidence). Similar rates of nocturnal and severe hypoglycemia were observed, rate ratio of 1.13 (95% CI 0.72 - 1.78; p = 0.54; 3 trials; 2668 patients; very low-certainty evidence) and 1.4 (95% CI 0.41 - 4.73; p = 0.59; 2 trials; 1952 patients; very low-certainty evidence), respectively. There is no evidence of a difference between IDeg and IGla-300 in the mean change in HbA1c and the risk of anytime, nocturnal, and severe hypoglycemia. IDeg appeared to cause a higher reduction in FPG compared to IGla-300. However, this finding should be interpreted with caution due to the small number of trials included and their high risk of bias. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364891, identifier CRD42022364891.

Role of Chia Seed (Salvia hispanica L.) Supplements in Managing Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Background: Chia seeds have been used traditionally for treating several diseases, including diabetes mellitus (DM). No meta-analysis has holistically analyzed and summarized the effect of chia seed supplementation on glycemic and metabolic parameters in patients with type 2 DM (T2DM); we conducted this meta-analysis to bridge this knowledge gap. Methods: Electronic databases were searched for clinical trials involving patients with T2DM receiving chia seeds in the intervention arm and control diet in the comparator arm. The primary outcome was the changes in glycated hemoglobin (HbA1c) from the baseline at the end of the trial. Results: From 60 initially screened articles, data from four randomized controlled trials involving 244 subjects were analyzed. Chia seed was not superior to control diets in HbA1c reduction (mean differences [MD] −0.09%, 95% confidence interval [CI] [−0.48, 0.29], P = 0.63, I 2 = 95%). It was inferior to control diets in fasting plasma glucose reduction (MD 0.27 mmol/L, 95% CI [0.17, 0.37], P &lt; 0.00001, I 2 = 0%). Chia seed was superior to the control diets regarding reductions in body weight (MD −1.58 mmol/L, 95% CI [−2.96,−0.20], P = 0.03, I 2 = 0%), systolic blood pressure (MD 13.15 mmHg, 95% CI [−22.18, −4.12], P = 0.004, I 2 = 0%) and diastolic blood pressure (MD −7.38 mmHg, 95% CI [−13.04, −1.72], P = 0.01, I 2 = 0%). Changes in C-reactive protein and lipid parameters were similar in the two groups. Conclusion: Current data do not support chia seeds’ glucose-lowering efficacy in patients with T2DM.

Four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: a systematic review and network meta-analysis

ObjectiveTo perform an evidence-based evaluation of the clinical efficacy of Taijiquan, Baduanjin, Yijinjing and Wuqinxi in interventions for type 2 diabetes.DesignA systematic review and network meta-analysis.MethodsThe comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpta Medica Database (Embase), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, VIP and China Biomedical Literature Database (CBM). Clinical randomized controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Taijiquan, Baduanjin, Yijinjing and Wuqinxi, were retrieved. The search time was conducted from the establishment of the database to 30 October 2022. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language, Stata and ADDIS statistical software programs were used to conduct statistics and analysis of intervention measures.ResultsA total of 33 randomized controlled trials with 2609 patients were identified. All patients were from China. The results of the network meta-analysis showed that Taijiquan ranked the best for improving HbA1c, 2-h postprandial blood glucose (2hPG), low-density lipoprotein cholesterol (LDL-C) and insulin sensitivity index indicator levels; Yijinjing reduced fasting plasma glucose (FPG) and total cholesterol (TC) indicator levels for the best probability ranking; Baduanjin improved the triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) probability ranking the most. When the training period was less than 12 weeks, Baduanjin had better effects in improving 2hPG, TC, TG, HDL-C and LDL-C indicator levels. Taijiquan had better effects in reducing FPG levels. When the training period was 12 weeks, the effect of Yijinjing in improving FPG, HbAlc, TC and HDL-C levels was better than that in other traditional Chinese exercise, and Taijiquan had better effects in improving 2hPG, TG and LDL-C indicator levels. When the training period was longer than 12 weeks, Taijiquan had better effects in improving FPG, HbAlc, 2hPG and LDL-C indicator levels, and Baduanjin had better effects in improving TC, TG and HDL-C indicator levels.ConclusionThe four traditional Chinese exercise therapies can improve blood glucose levels, blood lipid levels and insulin-related indicators of type 2 diabetes to varying degrees. Studies have shown that Taijiquan has a better targeted treatment effect on type 2 diabetes.Systematic review registrationCRD42020214786.Protocol publishedWe published the protocol article “Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: Protocol for a systematic review” in the BMJ Open magazine 2021, Issue 11, Volume 7.

Reductions in liver enzymes are associated with anti-hyperglycaemic and anti-obesity effects of tofogliflozin in people with type 2 diabetes: Post-hoc analyses.

How the pathology of type 2 diabetes (T2D), including hyperglycaemia and obesity, affects liver enzymes has not been clinically demonstrated. Thus, we compared time courses of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) with those of fasting plasma glucose (FPG) and body weight (BW) during treatment with the SGLT2 inhibitor tofogliflozin for T2D. We post-hocanalysed preexisting data on 1046 people with T2D administered tofogliflozin or placebo for 24 weeks in four tofogliflozin studies. First, time courses of percent changes in variables during the intervention were analysed using a mixed effect model to explore the similarity of the time courses and to evaluate time-treatment interactions. Second, clinical factors related to the percent changes in GGT and ALT were clarified using multivariate analyses. GGT levels and FPG values rapidly and significantly decreased via tofogliflozin as early as week 4, with decreases maintained until week 24. Conversely, BW and ALT decreased progressively until week 24. Time courses of FPG (p = .365, time-treatment interaction) and GGT (p = .510) reductions were parallel between tofogliflozin and placebo from weeks 4 to 24, while BW and ALT reductions (p < .001, respectively) were not. Reductions in GGT at week 24 were associated with reductions in FPG and BW at week 24, whereas ALT reductions were only associated with reductions in BW. Reductions in GGT and ALT were associated with the anti-hyperglycaemic and anti-obesity effects of tofogliflozin, respectively, in people with T2D. Therefore, GGT and ALT may be surrogate markers for hyperglycaemia and obesity in T2D.

Once-weekly Insulin Icodec as Compared to Once-daily Basal Insulins: A Meta-analysis

BackgroundOnce-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials. MethodsSeven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included. Based on available information, outcomes in terms of HbA1c, fasting plasma glucose reduction, and increase in time in range (TIR) were compared. Side-effects were compared for overall hypoglycemia, severe hypoglycemia, and weight gain. The pooled effect size for continuously distributed data was measured as a reduction in “estimated differences in mean (with 95% CI).” For categorical data, the pooled effect size was measured as the Mantel-Haenszel risk ratio (with 95% CI). ResultsAnalyzing against the nonicodec comparators together, the “estimated mean changes” in HbA1c and fasting plasma glucose favoring icodec were −0.22% (−0.35, −0.10) and −1.59 mg% (−9.26, 6.08) respectively. The “estimated mean increment” in weight for icodec was 0.64 kg (0.61, 0.67). The “estimated mean percentage” increment in TIR for icodec was 4.24% (2.99, 5.49). The Mantel-Haenszel risk ratios for all hypoglycemic events and severe hypoglycemia for icodec were 1.24 (1.02, 1.50) (P = .03) and 0.81 (0.31, 2.08) (P is not significant), respectively, suggesting a 24% increased incidence of all hypoglycemia with icodec. ConclusionOnce-weekly basal insulin icodec as compared to once-daily basal insulin analogs had a slight increase in the risk of overall hypoglycemia and weight gain, without any difference in severe hypoglycemia, with similar glycemic control (in terms of fasting plasma glucose, HbA1c, and TIR).

Fasting and postprandial plasma glucose contributions to hemoglobin A1c and time in range in people with diabetes on multiple daily injection insulin therapy: Results from the PRONTO-T1D and PRONTO-T2D clinical trials

AimsTo investigate contributions of changes in fasting plasma glucose (FPG) and postprandial glucose (PPG) to changes in hemoglobin A1c (HbA1c) and time-in-range (TIR, 70–180 mg/dL) in people with type 1 diabetes (T1D) and type 2 diabetes (T2D) treated with multiple daily injections (MDI) of insulin lispro (rapid/ultra-rapid formulations). MethodsMultivariate regression models were used to quantify the contributions of FPG and PPG reductions to change in HbA1c and TIR using data from the PRONTO-T1D (N = 1222) and PRONTO-T2D (N = 673) clinical trials. TIR was derived from 10-point self-monitored blood glucose (SMBG) profiles overall, as well as from continuous glucose monitoring (CGM) in the PRONTO-T1D CGM substudy (n = 269/1222). ResultsA 1 mmol/L FPG reduction corresponded with a 0.09–0.12 % (95 % confidence interval [CI] 0.06–0.15 %) HbA1c reduction in PRONTO-T1D and 0.17–0.26 % (95 % CI 0.13–0.30 %) in PRONTO-T2D (both p < 0.0001). A 1 mmol/L PPG reduction corresponded with a 0.05–0.09 % (95 % CI 0.01–0.12 %) HbA1c reduction in PRONTO-T1D (p < 0.001) and 0.10–0.15 % (95 % CI 0.05–0.19 %) in PRONTO-T2D (p < 0.0001). Reductions in FPG and PPG were significantly associated with increased TIR whether derived from SMBG (7.87–12.95 % [95 % CI 6.81–14.23 %]; all p < 0.0001) or CGM (3.35–4.18 % [95 % CI 2.11–5.39 %]; all p < 0.05). ConclusionsFPG and PPG significantly impact HbA1c and TIR. Balanced management of both FPG and PPG is important to achieve glycemic goals for people with diabetes on MDI insulin therapy. Clinical trials registrationPRONTO-T1D ClinicalTrials.gov identifier: NCT03214367; PRONTO-T2D ClinicalTrials.gov Identifier: NCT03214380

Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial.

Introduction: There is an increasing interest in using metformin in cardiovascular diseases and its potential new roles. Only two randomized controlled trials investigated the effect of metformin in nondiabetic heart failure (HF) patients. However, none of these studies assess the role of metformin in reducing oxidative stress. We hypothesized that metformin might improve oxidative stress and left ventricular remodeling in nondiabetic HF patients with reduced ejection fraction (HFrEF). Methods and Methods: Seventy HFrEF patients (EF 37% ± 8%; median age 66 years) were randomized to metformin (n = 35) or standard of care (SOC) for HF (n = 35) for 6 months in addition to standard therapy. Outcomes included the difference in the change (Δ) in total antioxidant capacity (TAC) and malondialdehyde (MDA), both assessed colorimetrically and left ventricular mass index (LVMI) assessed through transthoracic echocardiography. Results: Compared with the SOC, metformin treatment increased TAC [Δ = 0.12 mmol/L, confidence intervals (95% CIs): 0.03-0.21; P = 0.007]. TAC increased significantly only in the metformin group (0.90 ± 0.08 mmol/L at baseline vs. 1.04 ± 0.99 mmol/L at 6 months, P < 0.05). Metformin therapy preserved LVMI (Δ = -23 g/m2, 95% CI: -42.91 to -4.92; P = 0.014) and reduced fasting plasma glucose (Δ = -6.16, 95% CI: -12.31 to -0.02, P = 0.047) compared with the SOC. Results did not change after adjusting for baseline values. Changes in MDA left ventricular ejection fraction (LVEF) and blood pressure were not significantly different between groups. Conclusion: Metformin treatment in HF patients with reduced LVEF improved TAC and prevented the increase in LVMI compared with the SOC. These effects of metformin warrant further research in HF patients without diabetes to explore the potential benefits of metformin. Trial Registration Number: This protocol was registered in ClinicalTrials.gov under the number NCT05177588.