Metformin: an inexpensive and effective treatment in people with diabetes and COVID-19?

Metformin: an inexpensive and effective treatment in people with diabetes and COVID-19? Comment

Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice

Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed. After general disappointment around CVOTs assessing safety of DPP-4 inhibitors (SAVOR, TECOS, EXAMINE) and the GLP-1 receptor agonist lixisenatide (ELIXA), the EMPA-REG Outcome trial and the LEADER trial have shown superiority of the SGLT2-I empagliflozin and the GLP-1RA liraglutide, respectively, on the 3-point MACE outcome (cardiovascular death, non-fatal myocardial infarction or stroke) and cardiovascular, as well as all-cause mortality. While available mechanistic studies largely support a cardioprotective effect of GLP-1, the ability of SGLT2 inhibitor(s) to prevent cardiovascular death was unexpected and deserves future investigation. We herein review the results of completed CVOTs of glucose-lowering medications and suggest a possible treatment algorithm based on cardiac and renal co-morbidities to translate CVOT findings into clinical practice

Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes

Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients' preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal-bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients' viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients. © 2014 Dardano et al

Optimal therapy of type 2 diabetes: a controversial challenge

Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of "successful" aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population

Patient-reported outcomes in elderly patients with type 2 diabetes mellitus treated with dual oral therapy: a multicenter, observational study from Italy

Objective: To assess patient-reported outcomes after two years of use of dual oral anti-diabetes drug (OAD) therapy in elderly people (≥65 years) with type 2 diabetes mellitus (T2DM) from Italy under real-life settings. Methods: 3-AGE was a prospective, non-interventional study in elderly people with T2DM inadequately controlled on metformin monotherapy (defined as glycated hemoglobin [HbA1c] 7.0–9.0%), in whom a second OAD was prescribed. Primary endpoint was to assess the physical and psychological symptoms associated with T2DM from baseline to 24 months using the Diabetes Symptom Check List revised (DSC-R) questionnaire. Patient's quality of life and health status, treatment satisfaction, consumption of healthcare resources, and physician satisfaction with treatment were also assessed (secondary endpoints) using validated questionnaires. Additionally, safety and clinical characteristics were also evaluated. Results: The mean age of the study population (N = 860) was 71.5 ± 5.2 years. Addition of a second OAD significantly (p p p Conclusion: Addition of a second OAD improved physical and psychological symptoms associated with T2DM and was well tolerated in elderly people under real-life settings

Type 2 Diabetes Mellitus. From the start – combination therapy

Modern treatment of T2DM requires a shift in paradigm with appropriate intensification of therapy from the very first time of diabetes diagnosis. This is supported by data showing how even a moderate delay in achieving good glycemic control can translate into a later increased risk of developing diabetic complications. The recognition of the complexity of the pathogenesis of T2DM leads to the appreciation of the importance of attacking the disease from different angles, i.e. simultaneous tackling of multiple mechanisms contributing to hyperglycemia. From the turn of century a growing number of new anti-hyperglycemic agents have been made available. As compared to the older ones, these new medicines have a more targeted mechanism of action as they act at the level of the specific pathophysiologic disturbances accounting the development and progression of hyperglycemia. Because of that drugs can be use in combination taking advantage of their complementary mechanisms of action and synergistic. If introduced earlier in the natural history of the disease combination therapy may contribute avoiding undesirable exposure to even mild chronic hyperglycemia and provide early benefits. With respect to that in this review we will discuss advantages, disadvantages and still unanswered questions related to the use of early combination therapy in type 2 diabetes

Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes

Dapagliflozin is associated with greater reductions in HbA1c and weight than saxagliptin in management of type 2 diabetes mellitus (T2DM). The present post hoc analyses compared the durability of these effects over short- and long-term follow-up in patients with T2DM who were inadequately controlled with metformin (≥1500 mg/day) and who were receiving either dapagliflozin (10 mg/day) or saxagliptin (5 mg/day). Failure of glycaemiccontrol was assessed using the slope of the change in HbA1c from baseline-over-time regression line (coefficient of failure [CoF]). CoF was compared directly (dapagliflozin vs saxagliptin) over the short term (NCT01606007, 24 weeks) and indirectly (placebo-adjusted) over the long term (NCT00528879 and NCT00121667, 102 weeks). A low CoF value indicated greater durability. CoF was lower for dapagliflozin versus saxagliptin over 18–24 weeks (−1.38%/year; 95% CI, −2.41 to −0.35; P =.009) and 20–102 weeks (−0.37%/year; 95% CI, −0.73 to −0.02; P =.04). Fewer dapagliflozin-treated patients versus saxagliptin-treated patients required rescue medication or discontinued the study because of failure to achieve glycaemic control at 24 weeks (3.4% vs 9.4%; P =.0191). In patients with T2DM who were inadequately controlled with metformin, dapagliflozin was associated with greater durability of glycaemic control than saxagliptin over 18–24 and 20–102 weeks

Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?

Since the UK Prospective Diabetes Study (UKPDS), metformin has been considered the first-line medication for patients with newly diagnosed type 2 diabetes. Though direct evidence from specific trials is still lacking, several studies have suggested that metformin may protect from diabetes- and nondiabetes-related comorbidities, including cardiovascular, renal, neurological, and neoplastic diseases. In the past few decades, several mechanisms of action have been proposed to explain metformin's protective effects, none being final. It is certain, however, that metformin increases lactate production, concentration, and, possibly, oxidation. Once considered a mere waste product of exercising skeletal muscle or anaerobiosis, lactate is now known to act as a major energy shuttle, redistributed from production sites to where it is needed. Through the direct uptake and oxidation of lactate produced elsewhere, all end organs can be rapidly supplied with fundamental energy, skipping glycolysis and its possible byproducts. Increased lactate production (and consequent oxidation) could therefore be considered a positive mechanism of action of metformin, except when, under specific circumstances, metformin and lactate become excessive, increasing the risk of lactic acidosis. We are proposing that, rather than considering metformin-induced lactate production as dangerous, it could be considered a mechanism through which metformin exerts its possible protective effect on the heart, kidneys, and brain and, to some extent, its antineoplastic action