Canadian Diabetes & Endocrinology Today

Cardiovascular Safety of Testosterone Replacement Therapy in Hypogonadal Men

Jagoda Kissock, MD, FRCPC — Mon, 25 Nov 2024 00:00:00 +0000

Testosterone replacement therapy (TRT) aims to restore serum testosterone levels in men with hypogonadism. Symptoms associated with hypogonadism include reduced libido, erectile dysfunction, fatigue, depression, and loss of muscle mass and bone density. The primary purpose of TRT is to alleviate these symptoms and improve quality of life by restoring serum testosterone levels to the physiological range.

The prevalence of hypogonadism in men increases with age, affecting approximately 2–5% of middle-aged and older men and up to 20% of elderly men. Despite its therapeutic benefits, the cardiovascular safety of TRT remains a topic of debate and investigation. Cardiovascular disease is a leading cause of morbidity and mortality among men, and any therapy that might influence cardiovascular risk requires careful evaluation. Early observational studies raised concerns about potential adverse cardiovascular outcomes associated with TRT. These findings prompted regulatory agencies to issue warnings and recommend further research. In response, more recent trials, including the TRAVERSE Study, have provided new insights into the relationship between TRT and cardiovascular health. This article aims to provide a review of recent evidence on the cardiovascular safety of TRT.

The Role of Bisphosphonate Drug Holidays in the Management of Osteoporosis

Sandra Kim, MD, FRCPC, Adrian Lau, MD, FRCPC — Mon, 25 Nov 2024 00:00:00 +0000

Osteoporosis is a chronic skeletal disorder of compromised bone strength leading to an increased risk of fragility fractures, particularly with advancing age. More than 2 million Canadians are living with osteoporosis, and osteoporotic fractures are associated with considerable morbidity, increased mortality, and high economic burden to the healthcare system. The ultimate goal of osteoporosis pharmacotherapy is to reduce the risk of fragility fractures.

Bisphosphonates are the most widely used first-line medications for osteoporosis due to their robust anti-fracture efficacy and favourable safety profile, as demonstrated in short-term randomized placebo-controlled trials of 3-years duration with fracture outcome assessed as the primary endpoint. However, the optimal duration of bisphosphonate therapy has been questioned regarding their long‑term efficacy and safety given their long half‑life in bone. Prolonged use is associated with very rare but serious adverse complications such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Moreover, while extension trials indicate that long‑term bisphosphonate therapy helps maintain bone density, the evidence supporting further fracture risk reduction with prolonged treatment is less convincing. Regarding concerns about rare adverse effects and the attenuated benefit-to-risk ratio with long‑term use, several professional organizations have issued guidelines suggesting bisphosphonate drug holidays. This approach aims to minimize prolonged exposure and mitigate rare risks while preserving some residual anti-fracture benefits from the persistent drug in the skeleton. Here, we review the role of bisphosphonate drug holidays in the long-term management of osteoporosis, the supporting evidence, recommended guidelines on treatment duration, along with key considerations for implementing a bisphosphonate drug holiday.

Treatment of Obesity in Individuals with Type 1 Diabetes

Mohammed Almehthel, MBBS, ABIM, CCD, FRCPC, Ali Alshehri, MD — Mon, 25 Nov 2024 00:00:00 +0000

The prevalence of obesity (OB) is increasing among individuals with type 1 diabetes (T1D), posing unique challenges for managing their blood sugar levels and long-term health. Unlike type 2 diabetes (T2D), which is closely linked to OB and insulin resistance (IR), addressing OB in T1D requires careful consideration, because patients rely on external insulin, which can contribute to weight gain. In this review, we will discuss the causes and complications of OB in individuals with T1D, current approaches to treatment, potential lifestyle, and medical, and surgical interventions to manage weight while effectively maintaining optimal blood sugar control.

Glucagon-like Peptide Receptor Agonists (GLP-1 receptor agonists): A Powerful Addition to Foundational Therapy Kidney Care in Patients with Type 2 Diabetes Mellitus

Louis P. Girard, MD, MBT, FRCPC — Mon, 25 Nov 2024 00:00:00 +0000

There has been a veritable explosion in therapeutic options for patients with chronic kidney disease (CKD) and Type 2 diabetes mellitus (T2DM). For the past several decades, therapy for this condition has been limited to glycemic control, blood pressure control and utilization of angiotensin converting enzyme inhibitors (ACEi’s) or angiotensin 2 receptor blockers (ARBs). Recently, the emergence of therapies with organ protective effects has completely altered the landscape of therapy and outcomes for CKD in T2DM. Specifically, several large randomized clinical trials have demonstrated the positive impact of sodium glucose luminal transporter 2(SGLT2) inhibitors on the progression of kidney disease, end-stage kidney disease (ESKD), major adverse cardiovascular events (MACE), cardiovascular (CV) death, hospitalization for heart failure(HHF), all‑cause hospitalization, and all-cause mortality. Furthermore, finerenone, a non-steroidal mineralocorticoid receptor (nsMRA), has also been established as a component of foundational kidney therapy in patients with T2DM. A robust clinical trial program demonstrated kidney protection, CV protection and reductions in HHF in patients with CKD and T2DM. International guidelines have been updated to incorporate these agents as standards of care in this group of patients. CKD in T2DM is a complex disease and it stands to reason that multi‑targeted therapy could result in better outcomes for patients, similar to the management of patients with chronic heart failure. Those who follow this field will have noted that GLP-1 receptor agonists are listed as a component of guideline-directed management. However, these recommendations are based on the CV protective effect of these agents. Until recently, it was not clear if GLP‑1RA’s possessed kidney protective properties. The recent publication of the FLOW trial confirms that GLP-1 receptor agonists are, in fact, kidney protective.

Monogenic and Syndromic Obesity: Therapeutic Implications

Stasia Hadjiyannakis, MD — Mon, 25 Nov 2024 00:00:00 +0000

Obesity is a complex, progressive and relapsing neuroendocrine condition, characterized by disordered communication between the gastrointestinal tract, adipocytes and the hypothalamus. It is a heterogeneous condition with unique etiologies, broadly classified as: polygenic obesity, monogenic obesity, syndromic obesity and secondary obesity.² The most common form of obesity is polygenic, a highly hereditable condition that involves the clustering of genes that increase the risk for obesity. This inherited genetic risk is exploited by socio-biologic exposures. Monogenic and syndromic obesity result from rare genetic mutations and are characterized by early onset severe obesity and hyperphagia. Secondary obesity may occur as a result of medication exposures, hypothalamic damage or primary endocrine disorders. Accurate classification of obesity is critical to inform surveillance and management strategies, decrease health risk and improve quality of life through newly available targeted therapies.