This Week in Endocrinology — Jul 31, 2026

Welcome to This Week in Endocrinology. This week we are covering ten notable papers spanning novel dual-acting incretin therapies and vascular diagnostics in diabetes, long-term management and complications in type 1 diabetes, and advanced diagnostic and therapeutic strategies in endocrine hypertension, oncology, and hormone-related disorders. Let's dive in.

We begin with a major double release in The Lancet investigating zenagamtide, a novel, unimolecular peptide agonist of glucagon-like peptide-1, amylin, and calcitonin receptors. In a thirty-six-week, phase two, dose-finding trial of two hundred sixty-two adults with type 2 diabetes on stable metformin, researchers evaluated once-weekly subcutaneous zenagamtide across six doses ranging from zero point four to forty milligrams [1]. Subcutaneous zenagamtide demonstrated significant, dose-dependent reductions in glycated hemoglobin, ranging from a decrease of zero point nine percent with the lowest dose to one point seven percent with the highest forty-milligram dose, compared to placebo [1]. Side effects were primarily mild-to-moderate gastrointestinal events, establishing a safety profile consistent with other incretin therapies [1]. Simultaneously, the investigators published a companion trial in The Lancet examining a once-daily oral formulation of zenagamtide in one hundred eighty-six adults with type 2 diabetes [2]. At thirty-six weeks, oral zenagamtide also achieved robust glycated hemoglobin reductions, ranging from zero point nine percent in the six-milligram group to one point four percent in the fifty-milligram group [2]. Gastrointestinal adverse events occurred in up to forty-seven percent of patients on the highest oral dose, highlighting that while both routes of administration are highly effective, oral delivery requires careful dose escalation [2]. While we continue to optimize glycemic control with these advanced agents, detecting macrovascular complications remains a critical challenge. A prospective, multicenter diagnostic accuracy study published in Diabetes Care evaluated five common bedside tests for peripheral arterial disease against computed tomography or magnetic resonance angiography in five hundred thirty-six patients with diabetes across sixteen sites in the United Kingdom [3]. Alarmingly, the sensitivity was extremely low across all bedside modalities: audible Doppler had a sensitivity of only thirty-six percent, visual Doppler was forty-two percent, the ankle-brachial pressure index was forty-one percent, and even the exercise ankle-brachial pressure index was forty-one percent [3]. The toe-brachial pressure index performed slightly better but still reached only fifty-five percent sensitivity [3]. These findings suggest that standard bedside vascular tests are highly unreliable for ruling out peripheral arterial disease in patients with diabetes, and clinicians should maintain a low threshold for advanced vascular imaging [3].

Turning to type 1 diabetes, a large-scale retrospective cohort study using the 2022 Nationwide Readmissions Database in the United States, published in The Journal of Clinical Endocrinology and Metabolism, evaluated the real-world impact of insulin delivery methods on inpatient outcomes [5]. Among over two hundred thirty thousand adult hospitalizations for type 1 diabetes, patients utilizing insulin pump therapy had a significantly lower thirty-day readmission rate of roughly fourteen percent, compared to over twenty percent for those using injectable insulin only [5]. Pump use was also associated with a reduced risk of in-hospital mortality, suggesting that supporting the continuation of personal insulin pumps during hospitalization, when clinically safe, can meaningfully improve patient outcomes and reduce healthcare utilization [5]. This focus on optimizing long-term survival is increasingly relevant as the population of older adults with type 1 diabetes expands. A comprehensive review in The Lancet Diabetes and Endocrinology highlights that while life expectancy has improved in high-income countries, clinicians must look beyond glucose and insulin to address the complex psychosocial, environmental, and healthcare system factors that affect older adults living with this condition [6]. Preventing chronic microvascular complications remains paramount, and a fifteen-year follow-up study in Diabetologia provides critical prognostic insights [9]. Investigators tracked eighty-seven patients with type 1 diabetes and baseline preserved kidney function to determine if cardiac autonomic neuropathy predicts renal decline [9]. After adjusting for confounders, baseline cardiac autonomic neuropathy was independently associated with an accelerated loss of kidney function, with patients experiencing a mean decline in estimated glomerular filtration rate of nearly fifteen milliliters per minute per one point seven three square meters, compared to a decline of only about three milliliters per minute in those without autonomic neuropathy [9]. This long-term association highlights the importance of early cardiovascular autonomic reflex testing to identify patients at elevated risk for diabetic kidney disease [9].

In the realm of endocrine hypertension and oncology, advanced imaging and targeted therapies are reshaping clinical management. A retrospective cohort study in The Journal of Clinical Endocrinology and Metabolism evaluated the utility of Gallium-sixty-eight-pentixafor positron emission tomography and computed tomography in primary aldosteronism surgery [4]. In a cohort of one hundred sixty-two patients undergoing unilateral adrenalectomy, a clearly unilateral scan demonstrated an outstanding positive predictive value of over ninety-eight percent compared to invasive adrenal venous sampling [4]. However, the study also revealed that twenty-six of eighty-two patients with confirmed unilateral aldosteronism on adrenal venous sampling had negative or bilateral imaging findings, particularly those with small or KCNJ5-nonmutated lesions [4]. This indicates that while a positive unilateral scan is highly reliable for ruling in surgical candidates, a negative or bilateral scan should not rule out surgery and still requires adrenal venous sampling [4]. Meanwhile, another review in The Journal of Clinical Endocrinology and Metabolism explores the emerging paradigm of theranostics in thyroid cancer [10]. The authors note that focal thyroid uptake of radiolabeled ligands targeting cell-surface proteins like somatostatin receptor type two or prostate-specific membrane antigen is associated with malignancy in nearly twenty percent of cases [10]. These diagnostic scans can successfully identify candidates with advanced, radioactive iodine-refractory thyroid cancer for peptide receptor radionuclide therapy, which has achieved disease control rates approaching sixty percent and is generally well-tolerated [10]. Moving to reproductive and metabolic endocrinology, a large cohort study of over four hundred thirteen thousand women with polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome, examined racial disparities in cardiovascular risk [8]. Published in The Journal of Clinical Endocrinology and Metabolism, the study found that while Black and Hispanic women initially appeared to have a higher risk of composite atherosclerotic cardiovascular disease compared to White women, the elevated risk for Black women became non-significant after fully adjusting for social determinants of health, such as homeownership, net worth, and education [8]. This underscores that socioeconomic and environmental factors, rather than biological differences alone, drive cardiovascular disparities in this patient population [8]. Finally, in male reproductive health, a cross-sectional study from the European Male Ageing Study, published in the European Journal of Endocrinology, investigated the relationship between testosterone and sexual function in five hundred twenty-six community-dwelling men [7]. Using liquid chromatography tandem mass spectrometry following equilibrium dialysis, researchers found that lower measured free testosterone was significantly associated with erectile dysfunction, decreased intercourse frequency, lower orgasm frequency, and reduced sexual desire, whereas total testosterone showed no association with any of these outcomes [7]. The study identified non-linear thresholds, with a steep increase in the probability of erectile dysfunction and low orgasm frequency occurring below free testosterone levels of one hundred sixty-three and one hundred thirty-eight picomoles per liter, respectively, highlighting the clinical necessity of measuring free testosterone directly when evaluating male sexual dysfunction [7].

If you only have time for one paper this week, make it the multicenter diagnostic accuracy study on peripheral arterial disease bedside tests published in Diabetes Care [3]. This study is a major wake-up call for clinical practice, demonstrating that traditional bedside assessments like the ankle-brachial pressure index and Doppler have unacceptably low sensitivity in patients with diabetes, meaning they cannot be trusted to rule out vascular disease and should prompt a lower threshold for advanced imaging.

Here are the key takeaways from this week in Endocrinology. First, the novel dual GLP-1 and amylin receptor agonist, zenagamtide, achieved clinically meaningful, dose-dependent glycated hemoglobin reductions in both once-weekly subcutaneous and once-daily oral formulations [1], [2]. Second, standard bedside diagnostic tests for peripheral arterial disease, including the ankle-brachial pressure index and Doppler, have poor sensitivity in patients with diabetes and should not be used to exclude a diagnosis [3]. Third, inpatient continuation of insulin pump therapy in adults with type 1 diabetes is independently associated with lower thirty-day readmission rates and reduced in-hospital mortality compared to injectable insulin regimens [5]. Fourth, the presence of baseline cardiac autonomic neuropathy is a strong, independent predictor of long-term kidney function decline and worsening albuminuria in type 1 diabetes [9]. Finally, directly measured free testosterone, rather than total or calculated free testosterone, is the key biomarker associated with male sexual dysfunction, with clear clinical thresholds identified at one hundred sixty-three and one hundred thirty-eight picomoles per liter [7].

That's your roundup for This Week in Endocrinology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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