Efficacy of DPP-4 inhibitors and SGLT2 inhibitors compared to sulphonylureas in adult patients with diabetes with low c-peptide levels with or without anti-GAD65 antibody positivity

: Patients with diabetes continued to exhibit a high risk for cardiovascular and renal events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF). The latter has recently been recognised as a major cause of morbidity and mortality in patients with diabetes mellitus. There had been an unmet need for drugs with cardiovascular (including HF) and renal protection, with an expectation that an ideal diabetic drug should improve these end points. Moreover, an ideal drug should have weight lowering benefits. Recently published outcome trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) can reduce cardiovascular and renal events, together with statistically significant weight reduction. As a result, many recently published international guidelines have recommended SGLT2 inhibitors and GLP-1RAs in patients with diabetes and pre-existing cardiovascular disease (CVD). In this review we will critically analyse the efficacy and cardiovascular (CV) safety of SGLT2 inhibitors, based on the available literature to help position them in the clinical decision process.

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A literature review and meta-analysis of safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus

Scientific Reports ◽

10.1038/s41598-021-92925-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Junichi Mukai ◽

Shinya Kanno ◽

Rie Kubota

Keyword(s):

Diabetes Mellitus ◽

Meta Analysis ◽

Japanese Patients ◽

Sglt2 Inhibitors ◽

Patients With Diabetes ◽

Language Restriction ◽

Calculated Risk ◽

Favorable Safety ◽

Type 1 Dm

AbstractThe safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors may depend on races/ethnicities. We aimed to assess the safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies with no language restriction from their inception to August 2019. Trials were included in the analysis if they were randomized controlled trials (RCTs) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM > 18 years and reporting HbA1c and at least 1 adverse event. We calculated risk ratios with 95% CIs and used a random-effects model. Of the 22 RCTs included in our review, only 1 included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparison with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatment with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, such as patients with different types of DM, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.

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Glycemia, Beta-Cell Function and Sensitivity to Insulin in Mildly to Critically Ill Covid-19 Patients

Medicina ◽

10.3390/medicina57010068 ◽

2021 ◽

Vol 57 (1) ◽

pp. 68 ◽

Cited By ~ 1

Author(s):

Ioannis Ilias ◽

Aristidis Diamantopoulos ◽

Maria Pratikaki ◽

Efthymia Botoula ◽

Edison Jahaj ◽

...

Keyword(s):

Insulin Secretion ◽

Beta Cell ◽

Critically Ill ◽

Beta Cell Function ◽

Cell Function ◽

Model Assessment ◽

Secondary Diabetes ◽

C Peptide ◽

Number Of Patients ◽

Patients With Diabetes

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes.

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Hyperglycemic Crises in Adult Patients With Diabetes: Response to Yasuda et al.

Diabetes Care ◽

10.2337/dc09-1563 ◽

2009 ◽

Vol 32 (12) ◽

pp. e158-e158 ◽

Cited By ~ 4

Author(s):

A. E. Kitabchi ◽

G. Umpierrez ◽

J. Miles ◽

J. Fisher

Keyword(s):

Adult Patients ◽

Patients With Diabetes

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Mo1579 Islet Autoantibodies and C-Peptide Levels in Patients With Diabetes and Symptoms of Gastroparesis

Gastroenterology ◽

10.1016/s0016-5085(16)32450-7 ◽

2016 ◽

Vol 150 (4) ◽

pp. S718 ◽

Cited By ~ 1

Author(s):

Carol Homko ◽

Kevin P. May ◽

Elias Siraj ◽

Ajaykumar Rao ◽

Henry P. Parkman ◽

...

Keyword(s):

Islet Autoantibodies ◽

C Peptide ◽

Patients With Diabetes

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Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study

10.2337/figshare.13244498 ◽

2020 ◽

Author(s):

Josefin E Löfvenborg ◽

Sofia Carlsson ◽

Tomas Andersson ◽

Christiane S Hampe ◽

Albert Koulman ◽

...

Keyword(s):

Plasma Phospholipid ◽

Fish Intake ◽

Adult Onset ◽

Onset Diabetes ◽

Dietary Fish ◽

Antibody Positivity ◽

Adult Onset Diabetes ◽

Gad65 Antibody ◽

High Fish ◽

Gad65 Antibodies

Objective: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid polyunsaturated omega-3 fatty acid (n-3 PUFA) concentration with GAD65 antibody positivity on the risk of developing adult onset diabetes. Research Design and Methods: We used prospective data on 11,247 incident cases of adult onset diabetes and 14,288 non-cases from the EPIC-InterAct case-cohort study, conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction; AP) and multiplicative interaction between GAD65 antibody positivity (≥65 U/ml) and low fish/n-3 PUFA were assessed. Results: The hazard of diabetes in antibody positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52, 95% CI 1.76-3.63; 2.48, 1.79-3.45) compared to people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44, 95% CI 0.16-0.72; 0.48, 0.24-0.72) and multiplicative (p=0.0465; 0.0103) interaction. Individuals with high GAD65 antibody levels (≥167.5 U/ml) and low total plasma phospholipid n-3 PUFA had more than 4-fold higher hazard of diabetes (HR 4.26, 2.70-6.72), AP 0.46 (0.12-0.80), compared to antibody negative individuals with high n-3 PUFA. Conclusions: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

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Management of Bacterial Urinary Tract Infections in Adult Patients with Diabetes Mellitus

Drugs ◽

10.2165/00003495-200262130-00003 ◽

2002 ◽

Vol 62 (13) ◽

pp. 1859-1868 ◽

Cited By ~ 15

Author(s):

Ruby Meiland ◽

Suzanne E. Geerlings ◽

Andy I.M. Hoepelman

Keyword(s):

Diabetes Mellitus ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Adult Patients ◽

Patients With Diabetes ◽

Tract Infections

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Bridging-type enzyme-linked immunoassay for zinc transporter 8 autoantibody measurements in adult patients with diabetes mellitus

Clinica Chimica Acta ◽

10.1016/j.cca.2015.05.010 ◽

2015 ◽

Vol 447 ◽

pp. 90-95 ◽

Cited By ~ 9

Author(s):

Gareth Dunseath ◽

Rossitza Ananieva-Jordanova ◽

Rebecca Coles ◽

Michael Powell ◽

Marie Amoroso ◽

...

Keyword(s):

Diabetes Mellitus ◽

Zinc Transporter ◽

Adult Patients ◽

Zinc Transporter 8 ◽

Patients With Diabetes

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The Efficacy of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors for the treatment of chronic diabetic macular oedema in vitrectomised eyes: a retrospective study

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2017-000130 ◽

2018 ◽

Vol 3 (1) ◽

pp. e000130 ◽

Cited By ~ 4

Author(s):

Hiroki Mieno ◽

Kazuhito Yoneda ◽

Masahiro Yamazaki ◽

Ryosuke Sakai ◽

Chie Sotozono ◽

...

Keyword(s):

Macular Oedema ◽

Sglt2 Inhibitor ◽

Diabetic Macular Oedema ◽

Sglt2 Inhibitors ◽

Rank Test ◽

Sodium Glucose Cotransporter ◽

Signed Rank ◽

Before And After ◽

Patients With Diabetes ◽

Signed Rank Test

ObjectiveTo investigate the change of chronic diabetic macular oedema (DMO) in vitrectomised eyes when the administration of sodium–glucose cotransporter 2 (SGLT2) inhibitors is initiated as a systemic medical treatment.Methods and analysisThis study involved 10 eyes of five patients with chronic DMO lasting more than 6 months who had previously undergone vitrectomy and whose systemic medical treatments were newly changed to SGLT2 inhibitors. In this study, chronic DMO was defined as persistent diffuse macular oedema despite ophthalmic treatment in patients with diabetes. Patients who received antivascular endothelial growth factor therapy or steroids administration, or change of eye-drop medication from at 3 months before and after the initiation of SGLT2 inhibitors, were excluded. In this study, visual acuity (VA) and central retinal thickness (CRT, μm) prior to and at 3, 6 and 12 months after the initiation of SGLT2 inhibitors were retrospectively compared. The Wilcoxon signed-rank test was used for statistical analysis.ResultsIn the 10 treated eyes, from at baseline to at 3, 6 and 12 months after the initiation of SGLT2 inhibitor, median VA (logMAR) improved from 0.35 to 0.15 (p=0.038), 0.2 (p=0.157) and 0.2 (p=0.096), respectively, and median CRT significantly reduced from 500.5 µm to 410 µm (p<0.01), 378 µm (p<0.01) and 339 µm (p<0.01), respectively.ConclusionAlthough this study involved only five patients, our findings indicate that SGLT2 inhibitors might have structural efficacy for chronic DMO in vitrectomised eyes.

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