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Background Aim Method Results Conclusion Dipeptidyl peptidase‐4 inhibitors (DPP4i) and sodium‐glucose co‐transporter 2 inhibitors (SGLT2i) are increasingly used as glucose‐lowering therapies in Malaysia.To examine factors associated with the initiation of DPP4i or SGLT2i among people with type 2 diabetes mellitus (T2DM) in Malaysia.A retrospective cohort study was conducted from 1 January 2012–30 December 2020 in two tertiary Malaysian hospitals. Multivariate logistic regression was used to assess the factors associated with DPP4i or SGLT2i initiation. The impact of treatment initiation on glycaemic control, anthropometric and lipid levels at 6 and 12 months were also measured. Ethical approval was granted by the Malaysian National Medical Research Register (Reference no: NMRR‐20‐662‐52570), the Monash University Human Research Ethics Committee (Reference no: 2020‐24900‐45575), the Ministry of Health Malaysia Medical Research and Ethics Committee, and the study conforms with the Declaration of Helsinki.This study included 1628 patients. Patients with co‐existing dyslipidaemia (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.04–1.73), cardiovascular disease (OR 1.43, 95% CI 1.1–1.87), and microalbuminuria (OR 2.47, 95% CI 1.42–4.3), with ≥5‐year history of T2DM (years of T2DM 5–14 OR 1.67, 95% CI1.18–2.38; years of T2DM ≥15 OR 2.07, 95% CI 1.39–3.07), who had a body weight of ≥100 kg (OR 1.75, 95% CI 1.26–2.45), and baseline use of three or more glucose‐lowering medicines (OR 2.92, 95% CI 1.74–4.91) had higher odds of being prescribed with SGLT2i. Patients aged ≥65 years old (OR 0.68, 95% CI 0.50–0.93), presented with a family history of diabetes (OR 0.64, 95% CI 0.47–0.89), an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (eGFR 60–89 mL/min/1.73 m2 OR 0.60, 95% CI 0.39–0.90; eGFR ≥90 mL/min/1.73 m2 OR 0.55, 95% CI 0.34–0.87), with serum creatinine ≥120 μmol/L (OR 0.31, 95% CI 0.17–0.58), and had baseline usage of sulfonylureas (OR 0.28, 95% CI 0.19–0.4) and insulin (OR 0.5, 95% CI 0.35–0.72) were more likely to receive DPP4i. Glycated haemoglobin of patients receiving these medicines reduced significantly at 6 months (DPP4i: −0.61%, p < 0.001; SGLT2i: −0.66%, p < 0.001) and 12 months (DPP4i: −0.62%, p < 0.001; SGLT2i: −0.74%, p < 0.001).Treatment choice with pharmacotherapy was associated with many clinical risk factors presented by patients. [ABSTRACT FROM AUTHOR]

Abstract Background Glycemic monitoring has become critical during the COVID-19 pandemic because of poor prognosis in diabetes. Vaccines were key in reducing the spread of infection and disease severity but data were lacking on effects on blood sugar levels. The aim of the current study was to investigate the impact of COVID-19 vaccination on glycemic control. Methods We performed a retrospective study of 455 consecutive patients with diabetes who completed two doses of COVID-19 vaccination and attended a single medical center. Laboratory measurements of metabolic values were assessed before and after vaccination, while the type of vaccine and administrated anti-diabetes drugs were analyzed to find independent risks associated with elevated glycemic levels. Results One hundred and fifty-nine subjects received ChAdOx1 (ChAd) vaccines, 229 received Moderna vaccines, and 67 received Pfizer–BioNtech (BNT) vaccines. The average HbA1c was raised in the BNT group from 7.09 to 7.34% (P = 0.012) and non-significantly raised in ChAd (7.13 to 7.18%, P = 0.279) and Moderna (7.19 to 7.27%, P = 0.196) groups. Both Moderna and BNT groups had around 60% of patients with elevated HbA1c following two doses of COVID-19 vaccination, and the ChAd group had only 49%. Under logistic regression modeling, the Moderna vaccine was found to independently predict the elevation of HbA1c (Odds ratio 1.737, 95% Confidence interval 1.12–2.693, P = 0.014), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) was negatively associated with elevated HbA1c (OR 0.535, 95% CI 0.309–0.927, P = 0.026). Conclusions Patients with diabetes might have mild glycemic perturbations following two doses of COVID-19 vaccines, particularly with mRNA vaccines. SGLT2i showed some protective effect on glycemic stability. Hesitancy in having vaccinations should not be indicated for diabetic patients with respect to manageable glycemic change. Trial registration Not applicable.

Background: Glycemic monitoring has become critical during the COVID-19 pandemic because of poor prognosis in diabetes. Vaccines were key in reducing the spread of infection and disease severity but data were lacking on effects on blood sugar levels. The aim of the current study was to investigate the impact of COVID-19 vaccination on glycemic control. Methods: We performed a retrospective study of 455 consecutive patients with diabetes who completed two doses of COVID-19 vaccination and attended a single medical center. Laboratory measurements of metabolic values were assessed before and after vaccination, while the type of vaccine and administrated anti-diabetes drugs were analyzed to find independent risks associated with elevated glycemic levels. Results: One hundred and fifty-nine subjects received ChAdOx1 (ChAd) vaccines, 229 received Moderna vaccines, and 67 received Pfizer–BioNtech (BNT) vaccines. The average HbA1c was raised in the BNT group from 7.09 to 7.34% (P = 0.012) and non-significantly raised in ChAd (7.13 to 7.18%, P = 0.279) and Moderna (7.19 to 7.27%, P = 0.196) groups. Both Moderna and BNT groups had around 60% of patients with elevated HbA1c following two doses of COVID-19 vaccination, and the ChAd group had only 49%. Under logistic regression modeling, the Moderna vaccine was found to independently predict the elevation of HbA1c (Odds ratio 1.737, 95% Confidence interval 1.12–2.693, P = 0.014), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) was negatively associated with elevated HbA1c (OR 0.535, 95% CI 0.309–0.927, P = 0.026). Conclusions: Patients with diabetes might have mild glycemic perturbations following two doses of COVID-19 vaccines, particularly with mRNA vaccines. SGLT2i showed some protective effect on glycemic stability. Hesitancy in having vaccinations should not be indicated for diabetic patients with respect to manageable glycemic change. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of medications that have been approved for the treatment of heart failure (HF) in patients with and without type-2 diabetes mellitus. It is important to be aware of the likely side effects of SGLT2i for their optimal use and enhanced patient safety. One such rare but potential side effect is the development of euglycemic diabetic ketoacidosis (EDKA). Objective: We present a case report of EDKA, in a patient who was started on empagliflozin – one of the SGLT2i – highlighting its presenting signs and symptoms, pertinent laboratory findings, differential diagnosis, treatment and outcome. To strengthen our findings and hypothesis, we conducted a literature review of other cases that used SGLT2i and found similar complications. This case report with review can help recognize the serious, potentially life-threatening complications of the new class of medication SGLT2i that has been incorporated into the current practice, and also help to take appropriate steps to mitigate its adverse effects and improve overall health outcomes in our patients. Conclusions: SGLT2i are increasingly used because of their favorable effects on mortality in the chronic HF patients along with its benefits of weight loss and blood pressure reduction. A potential underdiagnosed adverse effect of SGLT2i use is diabetic ketoacidosis in a setting of normal blood glucose levels. Thus, it is reasonable to be cognizant of its side effects to prevent any untoward events in a timely manner.

Abstract Aims We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. Methods and results Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow‐up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2. Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2), the prescription rates of sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase‐4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non‐cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient‐years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27–0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28–0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. Conclusions Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.

Introduction: This prospective pharmacodynamic (PD) study assessed the effect of the sodium-glucose co-transporter-2 inhibitor (SGLT2i), dapagliflozin, on platelet reactivity. Methods: Patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) (n = 27) who were on maintenance dual antiplatelet therapy (DAPT) of aspirin 81 mg daily, and clopidogrel 75 mg daily were recruited. Platelet function was evaluated with the VerifyNow™ P2Y12 assay (Werfen, Bedford, MA, USA) and assessed prior to initiation of and after 10 days of treatment with dapagliflozin 10 mg once-daily dose regimen. Results were compared with a paired t test. Results: Treatment with dapagliflozin significantly decreased P2Y12 reaction units (PRU) by 20%, (95% confidence interval (CI) 8.5–32.6%, p value 0.002). The mean difference in PRU was 36.70 (95% CI 16.66–56.75). No patients experienced any serious adverse events (SAEs). Conclusions: Significantly diminished platelet reactivity was observed on dapagliflozin as compared to without dapagliflozin. This dedicated pharmacodynamic study could be potentially informative and applicable for Trinidadian stable CAD patients with T2DM on DAPT. Further studies are required to confirm these exploratory findings. Clinical Trial Registration: EDGE ClinicalTrials.gov number NCT04400760. [ABSTRACT FROM AUTHOR]

Aims: We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. Methods and results: Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow‐up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2. Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2), the prescription rates of sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase‐4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non‐cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient‐years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27–0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28–0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. Conclusions: Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients. [ABSTRACT FROM AUTHOR]

Objective: The use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) may be associated with ketoacidosis. Therefore, the associated risk factors should be identified. In particular, information regarding the effects of the co-administration of anti-diabetic drugs is lacking., Methods: We performed a retrospective study of 68 consecutive patients with diabetes who were taking an SGLT2i and attending a single medical center. After a period of treatment (median 78 days), their circulating ketone concentrations were measured. The concomitant use of other anti-diabetic drugs was analyzed to identify independent risk factors associated with ketosis., Results: Twenty-five participants were taking empagliflozin, 23 were taking dapagliflozin, and 20 were taking canagliflozin. During the treatment period, no ketoacidotic events were recorded and their mean circulating ketone concentrations at the end of the study period were similar (0.3 mmol/L in the empagliflozin group, 0.26 mmol/L in the dapagliflozin group, and 0.25 mmol/L in the canagliflozin group). After adjustment for the use of anti-diabetic drugs, pioglitazone was found to be independently associated with a risk of high circulating ketone concentration (B value: 0.361, 95% confidence interval: 0.181-0.541)., Conclusion: SGLT2i-associated ketoacidosis was found to be infrequent, but the concomitant use of pioglitazone was associated with a higher risk of ketosis.

Treatment intended to lower cardiovascular (CV) risk in patients with diabetes has always been a primary goal of diabetes treatment. Due to the subdued effects of reducing hemoglobin A1c (HbA1c) on macrovascular complications, controlling other CV risk factors such as hypertension and hyperlipidemia instead of hyperglycemia has been the mainstay treatment to improve CV outcome in patients with type 2 diabetes mellitus (T2DM) until recent years. This review is intended to summarize and compare the results from the available cardiovascular outcome trials (CVOTs) for the two classes of glucose lowering drug: sodium-glucose co-transporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). The results including the EMPA-REG, CANVAS program and DECLARE-TIMI 58 trials for SGLT2i, and the ELIXA, LEADER, SUSTAIN-6, EXSCEL and HARMONY trials for GLP-1 RA were summarized. The potential mechanisms of these CV beneficial effects and the optimal CV risk reduction treatment in patients with T2DM based on patient risk stratification and evidence from these CVOTs in real-world setting were discussed.