Major Hypoglycemia Research Articles

A comparison of the safety and effectiveness of insulin aspart with other bolus insulins in women with pre-existing Type 1 diabetes during pregnancy: A post hoc analysis of a prospective cohort study.

The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting. This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations. There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046). No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.

Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study.

Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48months of IDegLira. We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48months. Overall, 156 patients (mean age 68years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40mg/dl and body weight was significantly reduced by an average of 7.7kg. Five patients (3.2%) interrupted therapy with IDegLira during 48months, and no severe hypoglycemia occurred. Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.

Exposure of Pregnancy to Pregestational Diabetes, Gestational Diabetes, and Antidiabetic Medications With Especial Focus on Major Congenital and Cardiac Malformations in Offspring.

The global prevalence of type 2 diabetes mellitus (T2DM) is increasing. T2DM is more common in patients with psychiatric disorders and those who take certain psychotropic drugs. T2DM occurs in 2%-7% of women of reproductive age. The prevalence of pregestational diabetes is 0.5%-2.4%, and that of gestational diabetes is 7%-28%, depending on geographical region. About 20%-50% of pregnancies, across the world, are unplanned; this figure is higher, at about 65%, in women with psychiatric disorders. As a result, many women of reproductive age who have diabetes, including women who do not know that they have diabetes, may unintentionally become pregnant, thus unknowingly exposing their pregnancy to diabetes and its treatment. Exposure of pregnancy to pregestational and gestational diabetes is associated with risks to the mother as well as risks to the child. Risks to the mother include obesity, hypertension, and preeclampsia. Risks to the child include spontaneous abortion, fetal death, macrosomia, major congenital malformations (MCMs), preterm delivery, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal respiratory distress syndrome. A recent large retrospective cohort study with data from 6 countries in Europe, Asia, and North America found that, in about 51,000 women with pregestational T2DM, neither MCMs nor cardiac malformations were more prevalent in offspring of children periconceptionally exposed to second-line antidiabetic treatments relative to exposure to insulin. These findings are reassuring but have limitations that are discussed. A reasonable conclusion from a reading of the reviewed literature is that pregestational and gestational diabetes are best treated during pregnancy, that insulin is a first-line treatment, that metformin is an increasingly accepted alternative, and that safety data on second-line antidiabetic treatments are, so far, reassuring.

Maltodextrin Use in Persistent Neonatal Hypoglycemia; Audit Report of a Single Center Experience

Background: Neonatal hypoglycemia is known to cause significant neuronal damage and poor neurodevelopmental outcomes. Consensus guidelines are lacking for the management of persistent neonatal hypoglycemia and hyperinsulinism which often requires high concentrations of dextrose and medications. Although used in the pediatric population with persistent hypoglycemia, only a few case reports are published regarding the use of Maltodextrin supplementation in persistent neonatal hypoglycemia due to transient hyperinsulinism. Objective: To audit the use of Maltodextrins in the management of persistent neonatal hypoglycemia due to transient hyperinsulinism in neonates. Audit design: A retrospective chart review (CERNER electronic data) of all cases with persistent neonatal hypoglycemia who received Maltodextrin supplementation for a period of 3½ years between July 2018 and December 2021. Results: A total of 18 neonates received Maltodextrin supplementation for neonatal hypoglycemia during the audit period. 16/18 (89%) neonates who received Maltodextrin supplementation were weaned off from intravenous dextrose within 1 week without major side effects or severe rebound hypoglycemia. Two out of 18 babies who received Maltodextrin needed Diazoxide supplementation for persistent hypoglycemia. Conclusion: The results of our audit are promising, yet further research and randomized controlled studies are needed to systematically evaluate the findings of this audit regarding Maltodextrin supplementation for the management of neonatal hypoglycemia with transient hyperinsulinism.

Early Metformin in Gestational Diabetes

Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Increased Derived Time in Range Is Associated with Reduced Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and Microvascular Events in Type 2 Diabetes: A Post Hoc Analysis of DEVOTE.

Time spent in glycemic target range (time in range [TIR]; plasma glucose 70-180 mg/dL [3.9-10.0 mmol/L]) as a surrogate endpoint for long-term diabetes-related outcomes requires validation. This post hoc analysis investigated the association between TIR, derived from 8-point glucose profiles (derived TIR [dTIR]) at 12 months, and time to cardiovascular or severe hypoglycemic episodes in people with type 2 diabetes in the DEVOTE trial. At 12 months, dTIR was significantly negatively associated with time to first major adverse cardiovascular event (P = 0.0087), severe hypoglycemic episode (P < 0.0001), or microvascular event (P = 0.024). A nonsignificant trend was seen toward association between 12-month hemoglobin A1c (HbA1c) and these outcomes, but this was no longer seen after addition of dTIR to the model. The results support targeting TIR >70% and suggest dTIR could be used in addition to, or in some instances in place of, HbA1c as a clinical biomarker. Trial registration details: ClinicalTrials.gov, NCT01959529.

Sulfonylureas as second line therapy for type 2 diabetes among veterans: Results from a National Longitudinal Cohort Study

AimsTo assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone. Materials and MethodsThis was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes. ResultsSwitching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7–19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively). ConclusionsSwitching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy.

Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review.

Cardiovascular outcome trials have demonstrated cardiovascular safety of glimepiride (a sulfonylureas) against dipeptidyl peptidase-4 inhibitor linagliptin. Gliclazide (another newer sulfonylureas) has shown similar glycemic efficacy and 50% decreased risk of hypoglycemia compared to glimepiride. Considering the absence of cardiovascular outcome trials for gliclazide, we decided to conduct a systematic review of the literature to assess the car-diovascular (CV) safety by assessing the risk for major adverse CV events and hypoglycemia risk of gliclazide vs linagliptin in patients with type 2 diabetes (T2D). This systematic review followed the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to analyze all the clinical studies published from 2008 that compared the two drugs in patients with T2D with no risk of CV disease (CVD). We included only evidence designated high quality by the Oxford Center for Evidence-based Medicine-Levels of Evidence. Eight clinical studies were included in the narrative descriptive analysis (gliclazide: 5 and linagliptin: 3). The CV safety of gliclazide in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial and of linagliptin in the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) and CARdiovascular Outcome study of LINAgliptin vs glimepiride in patients with T2D (CAROLINA) trials were excluded from the comparative analysis as these trials demonstrated CV and hypoglycemia benefits in patients at high risk of CVD. However, since these are landmark trials, they were discussed in brief to show the CV benefits and low hypoglycemia risk of gliclazide and linagliptin. We did not find any study comparing gliclazide with linagliptin. Hence, direct comparison of their major adverse CV events and hypoglycemia risk could not be carried out. However, the literature meeting the inclusion criteria showed that both drugs were effective in achieving the desired glycemic control and had low major adverse CV events and hypoglycemia risk in adult patients with no history of CVD. Gliclazide can be considered an effective and safe glucose-lowering drug in T2D patients with no established CVD but at high risk of CVD due to their T2D status. Future randomized controlled trials comparing gliclazide with linagliptin or dipeptidyl peptidase-4 inhibitors can confirm these findings.

221-OR: Safety and Effectiveness of Insulin Aspart vs. Other Bolus Insulins in Women with Preexisting Type 1 Diabetes during Pregnancy: A Post Hoc Analysis of the EVOLVE Study

Aims: This post hoc analysis of the real-world EVOLVE study investigated safety and effectiveness of insulin aspart (IAsp) vs. other bolus insulins in pregnant women with pre-existing type 1 diabetes. Methods: Maternal, pregnancy and infant outcomes were assessed in women receiving bolus insulins on enrolment and during pregnancy in a prospective cohort, by estimating risk differences following adjustment for potential confounders using propensity score matching. Results: Insulin treatment in early pregnancy and maternal, pregnancy and infant outcomes are presented (Table) . In total, 1434 women were treated with IAsp and 4with other bolus insulins on enrolment. Significantly lower mean A1c values in the third trimester were observed with IAsp vs. other bolus insulins (adjusted % point difference -0.16% [95% CI -0.28;-0.05]; p=0.005) . No significant differences were seen with IAsp vs. other bolus insulins in the risk of adverse maternal-fetal outcomes including major maternal hypoglycemia, abortion, pre-term delivery, pre-eclampsia, birthweight large for gestational age, major congenital malformations and perinatal or neonatal death, in the matched dataset. Conclusion: Compared with other bolus insulins, IAsp was associated with significantly lower A1c during the third trimester and a similar risk of adverse pregnancy outcomes. Disclosure E.Mathiesen: Consultant; Novo Nordisk A/S, Speaker's Bureau; Novo Nordisk A/S. On behalf of the evolve study group: n/a. A.Alibegovic: Employee; Novo Nordisk A/S, Novo Nordisk A/S. G.Anil: Employee; Novo Nordisk Global Business Services. F.P.Dunne: None. T.Halasa: Employee; Novo Nordisk A/S. M.Ivanisevic: None. D.R.Mccance: None. R.Baastrup nordsborg: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. P.Damm: Advisory Panel; Novo Nordisk A/S. Funding Novo Nordisk A/S

Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality in Postpancreatitis Diabetes Mellitus Versus Type 2 Diabetes: A Nationwide Population-Based Cohort Study.

Postpancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and associates with poor glycemic control. We investigated the risk of adverse diabetes-related outcomes in PPDM compared with type 2 diabetes. In this Danish population-based cohort study, we included adults (>18 years) with incident PPDM or type 2 diabetes between 1998 and 2018 through national health registries. PPDM was further divided into acute (PPDM-A) and chronic (PPDM-C) subtypes. We ascertained risk of major adverse cardiovascular events (MACE), severe hypoglycemia, and all-cause mortality as well as incidence rates of severe hypoglycemia. We compared risk and incidence rates across diabetes subgroups using multivariate Cox and Poisson regression analyses. We identified 383,325 people with incident type 2 diabetes, 3,418 with PPDM-A, and 2,461 with PPDM-C. Compared with type 2 diabetes, PPDM-C was associated with increased risks of severe hypoglycemia (hazard ratio [HR] 5.27, 95% CI 4.62-6.00, P < 0.001) and all-cause mortality (HR 1.54, 95% CI 1.45-1.64, P < 0.001). Similar patterns were observed for people with PPDM-A. Incidence rate ratios (IRRs) for severe hypoglycemia were increased in both PPDM-C (IRR 7.38, 95% CI 6.75-8.08, P < 0.001) and PPDM-A (IRR 3.76, 95% CI 3.36-4.21, P < 0.001) compared with type 2 diabetes. Findings were consistent in an analysis restricted to people on insulin and in an analysis including pancreatitis patients without diabetes as comparator group. Compared with type 2 diabetes, PPDM is associated with excess risk of adverse diabetes-related outcomes. This has important implications for management.

Evidence-based risk factors for major complications during Ramadan fasting in people with diabetes grouped under IDF-DAR risk categories

AimTo identify evidence-based risk factors for major complications during Ramadan fasting in people with diabetes grouped under IDF-DAR risk categories. MethodsThis prospective observational multicenter study was conducted by Baqai Institute of Diabetology and Endocrinology (BIDE) between April-June 2019. People with diabetes having intention to fast during Ramadan were recruited. Demographic data collection along with risk categorization was done during pre-Ramadan visit. Structured education was given on one- to-one basis to each of the study participants. Assessment of complications was done during post Ramadan visit. ResultsA total of 1045 people with diabetes participated with near equal gender distribution. Two thirds of study population was grouped into very high- and high-risk categories. Frequencies of major hypoglycemia, major hyperglycemia, hospitalization & need to break the fast were 4.4%, 10.8%, 0.8% & 3.1% respectively.On multivariate analysis, the risk factors found for major hypoglycemia during Ramadan were male gender, use of sedatives & antidepressants & having type1 diabetes mellitus, history of DKA/HHS during last 3 months for major hyperglycemia, major hypoglycemia & hospitalization for breaking of fast while older age, acute illness, and major hypoglycemia were identified factors for hospitalization. ConclusionIn this prospective study evidence-based risk factors for fasting related major complications were identified in people with diabetes. It is imperative to recognize these factors during pre-Ramadan risk assessment visit.

The Safety and Efficacy of Combination Therapy of Dapagliflozin and Metformin in Patient with Type 2 Diabetes Mellitus: A Review Study

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class that approved by FDA for patient with type 2 DM. Dapagliflozin alone or in combination therapy with metformin provided effective glycemic control and HbA1c reduction, with minimal hypoglycemia and hypotension adverse effects. Objective: To evaluate the safety and efficacy of the combination therapy of dapagliflozin and metformin in type 2 diabetes mellitus patients. Methods: Research was conducted through MEDLINE and Embase databases in search of randomized controlled studies including dapagliflozin, sodium glucose co-transporter 2, metformin, and efficacy. Results: Forty seven articles were spotted, 3 randomized controlled studies were involved in this review. Dapagliflozin and metformin combination was found beneficial in HbA1c reduction equal to 20.7% - 31.5% from the baseline compared to patients on metformin alone. 40.6% of patients on combination therapy achieved the ADA recommended reduction in HbA1c to less than 7%. Moreover fasting plasma glucose level was reduced by 23.4 mg/dl from the baseline in the combination therapy compared to 5.9 mg/dl in metformin group. Body weight reduction was statistically significant (P < 0.0001) in the combination group. Moreover reduction in patient’s waist circumference was observed to be greater in all combination groups compared to MET group. Mild intensity of adverse effects such as major hypoglycemia, hypotension, or incidence of electrolyte changes was perceived. Therapy discontinuation was less likely with combination group. While UTI and genital infection were observed at higher extent in combination group than MET group. Conclusion: The combination therapy of dapagliflozin and metformin found to be safe and effective in type 2 diabetes mellitus management with minimal adverse effects.

Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis.

Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy. Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo. Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

Outcome trial data on sodium glucose cotransporter-2 inhibitors: Putting clinical benefits and risks in perspective

BackgroundSodium glucose cotransporter-2 (SGLT2) inhibitors have significant heart failure and renoprotective benefits with a wide spectrum of unfamiliar and potentially serious adverse effects. Limited understanding of the risk-benefit profile of SGLT2 inhibitor treatment may result in under utilisation by prescribers and patients. MethodsData from recent seminal randomized, placebo-controlled, outcome trials for multiple SGLT2 inhibitors were incorporated. Trial populations were sub-classified into high cardiovascular risk T2DM, HFrEF, and CKD. Efficacy outcomes of heart failure hospitalisation (HFH), cardiovascular (CV) mortality, total mortality, and prevention of renal deterioration were examined. Safety outcomes included were major hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infections (UTI), mycotic genital infections (MGI), hypotension, amputations and fractures. Absolute risk reduction/increase were used to calculate number needed to treat/harm. ResultsTrial data comprised 71,545 patients, of which 53,144 were high risk T2DM, 9696 HFrEF and 8705 CKD. For HFrEF, NNT for HFH was 18, CV mortality 93, total mortality 76, prevention of renal deterioration 143 and prevention of DKA 6224. NNH for UTI was 557, MGI 356, hypotension 120, hypoglycaemia 574, amputations 707 and fractures 858. For CKD, NNT for HFH was 116, CV mortality 245, total mortality 138, and prevention of renal deterioration was 63. NNH for DKA was 1458, UTI 309, MGI 291, hypotension 165, hypoglycaemia 374, amputations 4450 and fractures 696. In the T2DM cohort, NNT for HFH was 139, CV mortality 851, total mortality 601 and prevention of renal deterioration 558. NNH DKA was 1525, UTI 239, MGI 69, hypotension 325, hypoglycaemia 472, amputations 1578 and fractures 9569. Conclusions and relevanceThe cardiovascular and renal protective benefits of SGLT2 inhibitors far outweigh the risks. This paper puts into perspective the benefits and risks of treatment with SGLT2 inhibitors for clinicians and patients.

In-Hospital Mortality and Glycemic Control in Patients with Hospital Hyperglycemia

BACKGROUNDStress-induced hyperglycemia is a phenomenon that occurs typically in patients hospitalized for acute disease and resolves spontaneously after regression of the acute illness. However, it can also occur in diabetes patients, a fact that is sometimes overlooked. It is thus important to make a proper diabetes diagnosis if hospitalized patients with episodes of hyperglycemia with and without diabetes are studied.AIMSTo estimate the extent of the association between stress-induced hyperglycemia and in-hospital mortality in patients with hospital hyperglycemia (HH), and to explore potential differences between patients diagnosed with diabetes (HH-DBT) and those with stress-induced hyperglycemia (SH), but not diagnosed with diabetes.METHODSA cohort of adults with hospital hyperglycemia admitted to a tertiary, university hospital in Buenos Aires, Argentina, was analyzed retrospectively.RESULTSIn the study, 2,955 patients were included and classified for analysis as 1,579 SH and 1,376 HH-DBT. Significant differences were observed in glycemic goal (35.53% SH versus 25.80% HH-DBT, p < 0.01), insulin use rate (26.66% SH versus 46.58% HH-DBT, p < 0.01), and severe hypoglycemia rate (1.32% SH versus 1.74% HH-DBT, p < 0.01). There were no differences in hypoglycemia rate (8.23% SH versus 10.53% HH-DBT) and hospital mortality. There was no increase in risk of mortality in the SH group adjusted for age, non-scheduled hospitalization, major surgical intervention, critical care, hypoglycemia, oncological disease, cardiovascular comorbidity, and prolonged hospitalization.CONCLUSIONSIn this study, we observed better glycemic control in patients with SH than in those with HH-DBT, and there was no difference in hospital mortality.

Role of glucagon-like peptide-1 agonist in patients undergoing percutaneous coronary intervention or coronary artery bypass grafting: A meta-analysis

ImportanceGlucagon-like peptide-1 (GLP-1) protects against ischemia-reperfusion injury in patients with acute myocardial infarction (AMI). Controversy exists on the effects of GLP-1 on AMI patients undergoing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. Study objectiveWe aimed to investigate the cardioprotective effects of GLP-1 in AMI patients after PCI and CABG. DesignWe searched PubMed, Web of Science, EBSCO, Scopus, and the Cochrane Library for relevant randomized controlled trials (RCTs) up to June 2021, with no restriction on publication date. The following search terms are used: “percutaneous coronary intervention” or “coronary artery bypass grafting” or “myocardial infarction” and “glucagon-like peptide 1” or “exenatide” or “liraglutide”. Study selectionArticles were independently assessed by 2 reviewers. We included RCTs only that compared GLP-1 with control in AMI patients. Data extraction and synthesisContinuous data were pooled as mean differences (MDs), while dichotomous variables were pooled as odds ratios (ORs), with 95% confidence interval (CI), using R software (meta package) for windows. Subgroup analysis according to the intervention type and GLP-agents were conducted. We assessed the heterogeneity among RCTs using the Q statistic and I2 statistic. We also tested publication bias by funnel plot–based methods. The quality of each study was assessed with the Cochrane risk of bias tool. Main outcomes and measuresPrimary outcomes were changes of left ventricular ejection fraction (LVEF), myocardial infarct characteristics, salvage index. Secondary outcomes included major adverse cardiac events (MACE), gastrointestinal events, and hypoglycemia. ResultsNine RCTs (14 reports) including 1216 patients were included in this meta-analysis. At 3 months follow up, GLP-1 was associated with improved LVEF (MD = 2.81, 95% CI [0.69, 4.94]), infarct size in grams (MD = −5.71, 95% CI [−10.24, −1.18]), and salvage index (MD = 0.09, 95% CI [0.05, 0.14]). While, GLP-1 had less MACE rate than control (RR = 0.64, 95% CI [0.41, 0.99]), and higher gastrointestinal side effects (RR = 4.21, 95% CI [2.39, 7.41]). Conclusions and relevanceThis meta-analysis illustrated that GLP-1 was associated with better LVEF and reduced infarct size in patients with AMI undergoing PCI and CABG surgery, although the mechanism on how this agent provide this benefit is not clear. Key pointsQuestion: What is the effectiveness of Glucagon-like peptide-1 (GLP-1) agonist in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery.Findings: This systematic review and meta-analysis illustrated that GLP-1 was associated with better left ventricular ejection fraction and reduced infarct size in patients with AMI undergoing PCI and CABG surgery, probably by reducing reperfusion injury.Meaning: GLP-1 could improve systolic and diastolic function, lowering the cardiovascular risk of morbidity and mortality in AMI patients.

CLINICAL EFFECTIVENESS OF FIXED DOSE COMBINATION OF EMPAGLIFLOZIN AND LINAGLIPTIN (EMPA/LINA) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS UNWILLING TO CONTINUE BASAL INSULIN THERAPY: A REAL-WORLD EXPERIENCE IN INDIAN SETTING

Many T2DM patients are reluctant to continue injectable insulin therapy affecting medication adherence. The objective was to investigate the clinical effectiveness with empagliozin/linagliptin (EMPA/LINA) combination in patients unwilling to continue insulin therapy. In this retrospective assessment, a total of 60 patients [(41 men, 19 women); age (± S.D.) 53.38 ± 8.49 years and disease duration 5.67±1.89 years; baseline HbA1c: 7.1±0.58%; BMI: 28.25±4.07 kg/m2 were initiated with EMPA/LINA (25/5 mg) after thorough assessment. During 12-week period, there was modest improvements in glycemic prole [baseline vs. endpoint; HbA1c: 7.1±0.58% versus 7.1±0.55% (p &lt; 0.63), FPG 129±14 mg/dl versus 125±9.3 mg/dl, PPG 154±18 mg/dl versus 143±11 mg/dl (p=0.01), proportion of patients achieving A1C goal with no major hypoglycemia was improved from 37% to 81.48%. The incidence of overall hypoglycemia was reduced. These ndings suggest that patients with stable glycemic status reluctant to continue insulin may have effective transition to EMPA/LINA therapy

All-cause mortality, cardiovascular mortality, major cardiovascular events and hypoglycaemia of patients with diabetes onset at an older age: results from the 10-year nationwide cohort study.

Longitudinal adverse outcomes are unclear among adults with diabetes according to the age of onset. To investigate the longitudinal diabetes-related outcomes in adults with new-onset diabetes stratified by age. Retrospective cohort study. Taiwan National Health Insurance Research Database claims data from 2000 to 2015. In total, 115,751 participants aged ≥40years with new-onset diabetes in 2003 were recruited and stratified by the ages 40-64 (64.3%), 65-74 (21.2%), 75-84 (11.8%) and ≥85years (2.7%) at the time of diagnosis. Time-varying multivariate Cox proportional hazards model adjusted for covariates was used to examine the associations between the ages of the patients at diabetes onset and the outcomes of interest [all-cause mortality, cardiovascular (CV) mortality, major cardiovascular events (MACE) and hypoglycaemia] during a 10-year follow-up period. The results showed that compared with those patients aged 40-64 at diagnosis, patients with older-onset diabetes had significantly higher comorbidities (P < 0.01) and a higher diabetes severity (P < 0.01). Patients with older-onset diabetes had a higher risk of all-cause mortality [adjusted hazard ratio (aHR) 2.28, 4.48 and 10.07 in 65-74, 75-84 and ≥85years old, respectively], CV mortality (aHR = 2.82, 6.06 and 15.91), MACE (aHR = 2.19, 3.01 and 4.15) and hypoglycaemia (aHR = 2.41, 3.59 and 4.62) than patients aged 40-64 during a 10-year follow-up period. Patients with diabetes onset at an older age was associated with increased risks of all-cause mortality, CV mortality, MACE and hypoglycaemia after adjusting for the severity of diabetes and anti-diabetic treatment.

Meta-Analysis on the Safety and Cardiorenal Efficacy of SGLT2 Inhibitors in Patients Without T2DM.

The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59–0.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40–0.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05–1.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.

Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial.

OBJECTIVEThe Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.RESEARCH DESIGN AND METHODSWe enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200–5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death.RESULTSOf 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes.CONCLUSIONSDapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.