Ranolazine Improves Glycemic Variability and Endothelial Function in Patients with Diabetes and Chronic Coronary Syndromes: Results from an Experimental Study

Background. Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Thus, we aimed to explore the effects of adding ranolazine to standard anti-ischemic and glucose-lowering therapy on long- and short-term GV as well as on endothelial function and oxidative stress in patients with T2D and CCS. Methods. Patients starting ranolazine ( n = 16 ) were evaluated for short-term GV, haemoglobin 1Ac (Hb1Ac) levels, endothelial-dependent flow-mediated vasodilation (FMD), and oxidative stress levels at enrolment and after 3-month follow-up. The same measurements were collected from 16 patients with CCS and T2D that did not receive ranolazine, matched for age, gender, and body mass index. Results. A significant decline in Hb1Ac levels was reported after 3-month ranolazine treatment (mean change -0.60%; 2-way ANOVA p = 0.025 ). Moreover, among patients receiving ranolazine, short-term GV indexes were significantly improved over time compared with baseline ( p = 0.001 for time in range; 2-way ANOVA p = 0.010 ). Conversely, no significant changes were reported in patients without ranolazine. Finally, greater FMD and lower oxidative stress levels were observed in patients on ranolazine at 3 months. Conclusions. Ranolazine added to standard anti-ischemic and glucose-lowering therapy demonstrated benefit in improving the glycemic status of patients with T2D and CCS. How this improvement contributes to the overall myocardial benefit of ranolazine requires further studies.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence?

Patients with Covid-19 place new challenges on the management of type 2 diabetes, including the questions of whether glucose-lowering therapy should be adjusted during infection and how to manage a return to normal care after resolution of Covid-19 symptoms. Due to the sudden onset of the pandemic, physicians have by necessity made such important clinical decisions in the absence of robust evidence or consistent guidelines. The risk to patients is compounded by the prevalence of cardiovascular disease in this population, which alongside diabetes is a major risk factor for severe disease and mortality in Covid-19. We convened as experts from the Central and Eastern European region to consider what advice we can provide in the setting of type 2 diabetes and Covid-19, considering the evidence before, during and after infection. We review recommendations that have been published to date, and consider the best available—but currently limited—evidence from large observational studies and the DARE-19 randomized control trial. Notably, we find a lack of guidance on restarting patients on optimal antidiabetic therapy after recovering from Covid-19, and suggest that this may provide an opportunity to optimize treatment and counter clinical inertia that predates the pandemic. Furthermore, we emphasize that optimization applies not only to glycaemic control, but other factors such as cardiorenal protection. While we look forward to the emergence of new evidence that we hope will address these gaps, in the interim we provide a perspective, based on our collective clinical experience, on how best to manage glucose-lowering therapy as patients with Covid-19 recover from their disease and return to normal care.

Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study

<p><i>Objective</i>: Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared to type 1 and type 2 diabetes.</p> <p><i>Research Design and Methods:</i> In a Danish nation-wide population-based cohort study we identified all individuals with adult-onset diabetes mellitus in the period 2000-2018 and categorized them as type 1 diabetes, type 2 diabetes or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. </p> <p><i>Results</i><i>:</i> Among 398,456 adults with new-onset diabetes mellitus, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years vs. 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence-rate-ratio 0.6; 95% CI 0.6-0.7, p<0.001). A sizeable proportion of PPDM patients were classified as type 2 diabetes (44.9%) and were prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared to type 2 diabetes (hazard ratio 3.10; 95% CI 2.96-3.23, p<0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30; 95% CI 4.01-4.56, p<0.001).</p> <p><i>Conclusions</i><i>:</i> PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.</p>

Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study

<p><i>Objective</i>: Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared to type 1 and type 2 diabetes.</p> <p><i>Research Design and Methods:</i> In a Danish nation-wide population-based cohort study we identified all individuals with adult-onset diabetes mellitus in the period 2000-2018 and categorized them as type 1 diabetes, type 2 diabetes or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. </p> <p><i>Results</i><i>:</i> Among 398,456 adults with new-onset diabetes mellitus, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years vs. 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence-rate-ratio 0.6; 95% CI 0.6-0.7, p<0.001). A sizeable proportion of PPDM patients were classified as type 2 diabetes (44.9%) and were prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared to type 2 diabetes (hazard ratio 3.10; 95% CI 2.96-3.23, p<0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30; 95% CI 4.01-4.56, p<0.001).</p> <p><i>Conclusions</i><i>:</i> PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.</p>

Analysis of the Adherence and Safety of Second Oral Glucose-Lowering Therapy in Routine Practice From the Mediterranean Area: A Retrospective Cohort Study

The aims of our study was compare adherence measured by the medical possession ratio (MPR), time until discontinuation and describe adverse events after adding a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in a primary care population with insufficient glycemic control. We used routinely-collected health data from the SIDIAP database. The included subjects were matched by propensity score. The follow-up period was up to 24 months or premature discontinuation. The primary outcomes were the percentage of subjects with good adherence, treatment discontinuation and adverse events among treatment groups. The proportion of patients with good adherence (MPR&gt; 0.8) after the addition of DPP-4i, SGLT-2i or SU was 53.6%, 68.7%, and 43.0%, respectively. SGLT-2i users were 1.7 times more likely to achieve good adherence compared with DPP-4i users (odds ratio [OR]:1.72, 98% confidence interval [CI]:1.51, 1.96), and 2.8 times more likely compared with SU users (OR: 0.35, 98% CI: 0.07, 0.29). The discontinuation hazard ratios were 1.43 (98%CI: 1.26; 1.62) and 1.60 (98%CI: 1.42; 1.81) times higher among SGLT-2i and SU users than DPP-4i users during the follow-up period. No differences were observed for adverse events among the treatment groups. In conclusion, in our real-world setting, the combination of SGLT-2i with metformin was associated with better adherence. The mean time until discontinuation was longer in the SGLT-2i group in comparison with the DPP-4i or SU groups.