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Chronic kidney disease associated with Type 2 diabetes is linked to significant increase in morbidity, reduced quality of life, and early death. Current guidelines recommend targets for the management of hyperglycemia, hypertension, and dyslipidemia but there remains a residual risk of chronic kidney disease progression and adverse cardiovascular outcomes in patients with Type 2 diabetes. The 2022 consensus report from the American Diabetes Association and Kidney Disease: Improving Global Outcomes support the use of sodium-glucose co-transporter 2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists to improve kidney and cardiovascular outcomes. Coordination between those working in the primary care setting and those in endocrinology and nephrology clinics may optimize the prevention of chronic kidney disease progression in patients with Type 2 diabetes. Nurse practitioners, physician assistants, and primary care physicians play an important role in making timely patient referrals to kidney specialists. This article explores the use of novel therapies capable of reducing the risk of cardiovascular disease and chronic kidney disease progression beyond what can be achieved with control of blood glucose, blood pressure, and lipid levels. It also discusses the importance of monitoring at-risk patients to facilitate early diagnosis and initiation of effective kidney-protective therapy.[Media: see text][Figure: see text].

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Cardiovascular disease (CVD) is a common and serious comorbidity of type 2 diabetes mellitus (T2DM), and cardiovascular (CV) risk assessment has become an important aspect of evaluating new therapies for T2DM before approval by the FDA. Since 2008, in order to establish safety, new therapies for T2DM have been required to demonstrate that they will not result in an unacceptable increase in CV risk. Studies performed for this purpose are termed CV outcome trials, or CVOTs. This article reviews CVOTs completed to date for the class of long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs; liraglutide, exenatide extended-release, albiglutide, dulaglutide, semaglutide injectable, semaglutide oral) and implications for clinical management of T2DM. All CVOTs have confirmed long-acting GLP-1RAs to be noninferior to (not worse than) placebo with regard to first occurrence of a primary outcome of three-point major adverse cardiovascular events (MACE; composite outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). Further, a number of the studies demonstrated a statistically significant reduction in primary outcomes of three-point MACE with GLP-1RA treatment compared with placebo. As a result, the product labeling for liraglutide, semaglutide injectable, and dulaglutide has been updated with an indication for reducing the risk of MACE in adults with T2DM and established CVD (all) or multiple CV risk factors (dulaglutide only). These findings have brought about an exciting paradigm shift from concern about not inflicting CV harm to the exciting prospect of reducing risks of CV outcomes. Major diabetes care guidelines now encourage early consideration of GLP-1RA use in patients with atherosclerotic CVD.

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Cardiovascular disease (CVD) is a common and serious comorbidity of type 2 diabetes mellitus (T2DM), and cardiovascular (CV) risk assessment has become an important aspect of evaluating new therapies for T2DM before approval by the FDA. Since 2008, in order to establish safety, new therapies for T2DM have been required to demonstrate that they will not result in an unacceptable increase in CV risk. Studies performed for this purpose are termed CV outcome trials, or CVOTs. This article reviews CVOTs completed to date for the class of long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs; liraglutide, exenatide extended-release, albiglutide, dulaglutide, semaglutide injectable, semaglutide oral) and implications for clinical management of T2DM. All CVOTs have confirmed long-acting GLP-1RAs to be noninferior to (not worse than) placebo with regard to first occurrence of a primary outcome of three-point major adverse cardiovascular events (MACE; composite outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). Further, a number of the studies demonstrated a statistically significant reduction in primary outcomes of three-point MACE with GLP-1RA treatment compared with placebo. As a result, the product labeling for liraglutide, semaglutide injectable, and dulaglutide has been updated with an indication for reducing the risk of MACE in adults with T2DM and established CVD (all) or multiple CV risk factors (dulaglutide only). These findings have brought about an exciting paradigm shift from concern about not inflicting CV harm to the exciting prospect of reducing risks of CV outcomes. Major diabetes care guidelines now encourage early consideration of GLP-1RA use in patients with atherosclerotic CVD.

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Insulin initiation and titration can be challenging for many primary care providers who are involved in the treatment of patients with type 2 diabetes. Despite the introduction of advanced insulin analogs and improvements in insulin delivery devices, many patients with type 2 diabetes continue to experience suboptimal glycemic control. With an increasing number of treatment options available, type 2 diabetes management is moving away from a "one-size-fits-all" approach and toward individualized treatment regimens based on particular patient needs. Given this, nurse practitioners, physician assistants, pharmacists, and certified diabetes educators are becoming increasingly valuable resources in busy primary care practices.

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The number of patients receiving a BMT is currently being used as a factor in the accreditation process in determining whether a center can provide a high-quality BMT. Such criteria particularly impact pediatric BMT centers as most of them perform a relatively small number of BMTs. To determine whether patient volume is a valid marker of pediatric BMT center's capabilities, the Pediatric Blood and Marrow Transplant Consortium (PBMTC) evaluated data from its registry to define the relationship between a pediatric transplant center's patient volume and day +100 mortality. The analyses evaluated 2575 transplants from 60 centers reporting to the PBMTC between the years 2002 and 2004. The volume-outcome relationship was evaluated while adjusting for 46 independent data categories divided between nine variables that were known- or suspected-mortality risk factors. We found no association between transplant center volume and day +100 mortality in several analyses. A calculated intraclass correlation coefficient also indicated that differences in individual transplant center volume contributed to only 1% of the variance in day +100 mortality within the PBMTC. The results of this study suggest that factors other than transplant center volume contribute to variation in day +100 mortality among pediatric patients.

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Incretin therapeutics address an unmet need in diabetes by effectively treating postprandial glycemia. In addition, they present interesting possibilities for future therapy as they were suggested in preclinical studies to have effects on pancreatic beta-cell neogenesis. When used in combination with metformin, sulfonylureas, or TZDs, GLP-1 analogs such as exenatide and DPP-IV inhibitors such as sitagliptin reduce A1C, fasting glucose levels, and postprandial glucose levels with few additional adverse events. Incretin therapeutics is a relatively young field, and much remains to be discovered. It is to be hoped that as trial data accumulate they will demonstrate that these agents will improve overall glycemic control in those with type 2 diabetes. The possibility that they may also be able to affect the course of this devastating metabolic disorder should also be fully explored.

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