Diabetes and Stroke: What Are the Connections?

Stroke is a major cause of death and long-term disability worldwide. Diabetes is associated with an increased risk of cardiovascular complications, including stroke. People with diabetes have a 1.5-2 times higher risk of stroke compared with people without diabetes, with risk increasing with diabetes duration. These risks may also differ according to sex, with a greater risk observed among women versus men. Several mechanisms associated with diabetes lead to stroke, including large artery atherosclerosis, cerebral small vessel disease, and cardiac embolism. Hyperglycemia confers increased risk for worse outcomes in people presenting with acute ischemic stroke, compared with people with normal glycemia. Moreover, people with diabetes may have poorer post-stroke outcomes and higher risk of stroke recurrence than those without diabetes. Appropriate management of diabetes and other vascular risk factors may improve stroke outcomes and reduce the risk for recurrent stroke. Secondary stroke prevention guidelines recommend screening for diabetes following a stroke. The diabetes medications pioglitazone and glucagon-like peptide-1 receptor agonists have demonstrated protection against stroke in randomized controlled trials; this protective effect is believed to be independent of glycemic control. Neurologists are often involved in the management of modifiable risk factors for stroke (including hypertension, hyperlipidemia, and atrial fibrillation), but less often in the direct management of diabetes. This review provides an overview of the relationships between diabetes and stroke, including epidemiology, pathophysiology, post-stroke outcomes, and treatments for people with stroke and diabetes. This should aid neurologists in diabetes-related decision-making when treating people with acute or recurrent stroke.

Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies.

AIM: To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, ≤ 6.5% or < 5.7%) with weight loss (≥ 5%, ≥ 10% or ≥ 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D). MATERIALS AND METHODS: Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2) or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52. RESULTS: The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide. CONCLUSIONS: Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups.

Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison.

AIM: To conduct an adjusted indirect treatment comparison (aITC) of the efficacy of tirzepatide 5/10/15 mg versus semaglutide 2 mg in patients with type 2 diabetes. MATERIALS AND METHODS: The primary analysis was a Bucher aITC of the change from baseline at week 40 in HbA1c (%) and body weight (kg). Aggregate data from the SURPASS-2 study that met the HbA1c inclusion criterion of the SUSTAIN FORTE study and from SUSTAIN FORTE metformin-only treated patients were used for primary analysis. RESULTS: The SURPASS-2 refined population comprised 238/245/240 and 240 participants for tirzepatide 5/10/15 mg and semaglutide 1 mg, respectively. The SUSTAIN FORTE metformin-only population comprised 222 and 227 participants for semaglutide 1 and 2 mg, respectively. In this aITC, tirzepatide 10 and 15 mg significantly reduced HbA1c versus semaglutide 2 mg with an estimated treatment difference (ETD) of -0.36% (95% confidence interval [CI] -0.63, -0.09) and -0.4% (95% CI -0.67, -0.13), respectively. Tirzepatide 10 and 15 mg significantly reduced body weight versus semaglutide 2 mg with an ETD of -3.15 kg (95% CI -4.84, -1.46) and -5.15 kg (95% CI -6.85, -3.45), respectively. There were no significant differences between tirzepatide 5 mg and semaglutide 2 mg on change from baseline in HbA1c and body weight. CONCLUSIONS: In this aITC, HbA1c and weight reductions were significantly greater for tirzepatide 10 and 15 mg versus semaglutide 2 mg and were similar for tirzepatide 5 mg versus semaglutide 2 mg. These findings provide comparative effectiveness insights in the absence of a head-to-head clinical trial.

Management of Type 2 Diabetes in People With Renal Impairment.

Diabetes is a progressive disease associated with micro- and macrovascular complications. Type 2 diabetes (T2D) is the leading contributor to chronic kidney disease (CKD) worldwide, which itself is associated with an increased burden of cardiovascular disease, increased risk of hypoglycemia, and increased risk of death beyond that caused by diabetes alone. In this video series available on The Journal of Family Practice website, the authors discuss how CKD in people with T2D is defined, potential consequences of CKD in this patient population, and how those with CKD and T2D should be identified, monitored, and treated. The authors discuss the best management approaches for CKD in those with T2D, including blood pressure control, renin-angiotensin-aldosterone system blockade, use of sodium-glucose cotransporter-2 inhibitors, and glycemic control. The importance of glycemic control in the prevention and reduction of CKD progression in people with T2D is reviewed, with an emphasis on the use of antihyperglycemic agents as renal function declines. Finally, the authors discuss the use of basal insulin in this patient population, emphasizing the importance of reaching glycemic control goals while minimizing hypoglycemia. They note that, in people with T2D and reduced renal function, second-generation basal insulin analogs have demonstrated comparable efficacy to first-generation basal insulin analogs in reducing HbA1c levels­but with less hypoglycemia.

Rosiglitazone maleate + metformin hydrochloride extend: review of an emerging compound.

Clinical practice guidelines from around the world have continued to highlight the importance of glycemic control in the prevention of diabetes complications. Despite the many tools available to achieve these targets, it remains a constant challenge for healthcare providers and patients alike. Rosiglitazone maleate + metformin hydrochloride extend is a new compound that has the advantage of the clinical experience and knowledge about the current version and the added benefit of being a once daily, single pill option. The existing version of rosiglitazone + metformin has been shown to effectively lower hemoglobin A1C, improve insulin sensitivity and minimize weight gain. It is expected that the new compound will also have similar features, with the added benefit of improved patient adherence given its once daily formulation.

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.

PURPOSE OF REVIEW: In 2001, the Adult Treatment Panel III of the National Cholesterol Education Program issued recommendations, which were updated in 2004 to reflect knowledge from five major clinical trials completed after 2001. This review discusses the results of key clinical trials released in 2005 and their potential impact on the guidelines. RECENT FINDINGS: Three major clinical trials, one subgroup analysis, and one meta-analysis were published in 2005 that can potentially affect the existing guidelines. The Treating to New Targets and the Incremental Decrease in End Points Through Aggressive Lipid Lowering trials demonstrated the incremental benefit of more aggressive low-density cholesterol lowering in stable coronary heart disease. The Cholesterol Treatment Trialists' Collaboration meta-analysis of statin trials supported the importance of low-density lipoprotein cholesterol reduction, irrespective of initial lipid profile, in reducing cardiovascular events. A subgroup analysis of the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid-Lowering Arm demonstrated statin benefits in diabetes, whereas the Fenofibrate Intervention and Event Lowering in Diabetes study failed to show overall treatment benefits with a fibrate in diabetes. SUMMARY: Lowering of low-density lipoprotein cholesterol remains central in reducing cardiovascular risk; however, the recent trials support a target of less than 2.0 mmol/l (<80 mg/dl), rather than the less than 1.8 mmol/l (70 mg/dl) suggested by the 2004 update, for all high-risk patients and not, as recommended previously, just for those with additional factors. For individuals with diabetes, recent data support the use of statin therapy, even in those at less than high risk. First-line therapy should remain statins and not fibrates.