In this week’s issue of The Savvy Diabetic: 

• • • Why MARD Is the Wrong Headline Metric for CGM Performance
    • Semaglutide Benefits Extend to Type 1 Diabetes
    • Five Biotech Companies Moving Past Daily Insulin Injections
    • The Emerging Role of GLP-1s in Inflammatory Diseases
    • MIT Researchers Develop Non-Invasive Glucose Monitor

Why MARD Is the Wrong Headline Metric for CGM Performance by James Causey for JamesCausey.substack.com, 28 December 2025.

Mean Absolute Relative Difference (MARD) has become the default shorthand for evaluating continuous glucose monitor (CGM) performance—not because it is clinically meaningful, but because it is convenient. It compresses vast amounts of heterogeneous data into a single, easy-to-compare number that looks authoritative in a table or press release.

Unfortunately, that simplicity comes at a cost. By averaging error across the full glucose range, MARD systematically obscures performance where accuracy matters most: hypoglycemia, rapid glucose transitions, and decision-critical moments. A CGM can post an impressive overall MARD while still underperforming at low glucose levels, during exercise, or in the post-prandial window—exactly the scenarios where patients, caregivers, and automated insulin delivery systems are most exposed to risk. 

The deeper problem is not that MARD exists, but that it is routinely overinterpreted. Differences of a few tenths of a percent—often well within the noise of study design, reference method bias, or glucose distribution—are frequently framed as meaningful performance advances, despite having no demonstrated impact on outcomes such as hypoglycemia avoidance, dosing safety, or time-in-range. 

The stakes are even higher as iCGMs become the primary sensing layer for automated insulin delivery. Algorithms do not experience averages; they react to individual data points, trends, and inflection errors in real time. A sensor that looks “excellent” by MARD can still introduce systematic low-glucose bias, lag during rapid change, or asymmetric error that meaningfully alters insulin dosing decisions. 

In other words, in an automated future, MARD is not just insufficient—it is potentially misleading.

Read more: Why MARD Is the Wrong Headline Metric for CGM Performance

Semaglutide Benefits Extend to Type 1 Diabetes by Scott Buzby for Healio.com/endocrinology. 23 June 2025.

Semaglutide improved time spent in the glycemic range and time below the rate, and reduced body weight, with a lower rate of hypoglycemia compared with placebo in patients with type 1 diabetes and obesity using an automated insulin delivery system.

Viral N. Shah, MD, professor, found that by week 26, among those assigned semaglutide vs. placebo, the difference remained significant after adjusting for weight loss during the trial of medicine in the division of endocrinology and metabolism and director of diabetes clinical research at Indiana University Center for Diabetes and Metabolic Diseases, presented results of the ADJUST-T1D trial at the American Diabetes Association Scientific Sessions that were simultaneously published in NEJM Evidence.  In an exploratory analysis, Shah and colleagues reported a 30% reduction in insulin dose by week 26 among those assigned semaglutide vs. placebo, which remained significant after adjusting for weight loss during the trial.

Read more: Semaglutide benefits extend to type 1 diabetes

A New Era in Diabetes: Five Biotech Companies Moving Past Daily Insulin Injections, reported by ManufacturingChemist.com, 2 January 2026.

Investment in metabolic disease has been shaken up dramatically after recent clinical trials achieved insulin independence rates of 83%. Late-2025 M&A activity reached record valuations as major pharmaceutical companies raced to secure curative platforms rather than symptom-management franchises. This pivot toward functional cures, rather than chronic insulin dependence, is now defining the strategic roadmaps of companies such as Avant Technologies, Novo Nordisk, Eledon Pharmaceuticals, Viking Therapeutics and Tandem Diabetes Care.

Analysts project the regenerative medicine market will surge from $37.98bn in 2025 to $88.85bn by 2030, driven by curative cell therapies now entering pivotal trials. Meanwhile, FDA expedited review pathways have awarded more than 350 designations across diabetes and metabolic diseases in the past three years, compressing clinical timelines by 30% and creating an urgent investment window as breakthrough therapies rush towards commercial launch.

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Avant Technologies is developing cell-based therapies for diabetes, ageing and chronic diseases using a proprietary encapsulation technology that protects genetically modified therapeutic cells from immune rejection.  The company operates through two strategic joint ventures focused on addressing massive global health markets.

• • • • • The first, Insulinova, is a partnership with SGAustria Pte., through which Avant is developing treatments for type 1 and insulin-dependent type 2 diabetes. 
        • Avant’s second joint venture, Klothonova, partners with Singapore-based Austrianova to develop anti-ageing therapies and treatments for age-related diseases that restore circulating α-Klotho levels using genetically modified human cells that overexpress the Klotho protein.  Research from the Mayo Clinic indicates that declining α-Klotho levels are linked to arterial stiffness, endothelial dysfunction and vascular calcification.

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Novo Nordisk submitted a New Drug Application to the FDA for once-weekly CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg), the first injectable GLP-1 receptor agonist and amylin analogue combination for weight management.

In the REDEFINE 1 Phase III trial, adults with obesity or overweight with weight-related comorbidities taking CagriSema lost an average of 23% body weight when evaluating the treatment effect. The FDA is expected to review the CagriSema application in 2026, with Health Canada granting the first approval outside the US in August 2025.

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Eledon Pharmaceuticals recently announced preliminary data from six patients with type 1 diabetes treated with tegoprubart following islet transplantation at UChicago Medicine. All six subjects achieved insulin independence after 1 or 2 transplants, with one patient maintaining an HbA1c as low as 4.7% for more than 15 months without exogenous insulin.

• • • • • “For years, clinicians have been working to find a new medication that can prevent rejection of islet cells while offering a better safety profile than calcineurin inhibitors, including tacrolimus, which remains the current standard of care but is often associated with debilitating metabolic, neurologic and cardiovascular toxicities,” said Dr. Piotr Witkowski, Director of the Pancreas and Islet Transplant Programme at UChicago Medicine.
        • The trial has been extended to 12 subjects, and Breakthrough T1D has committed to fund a second study in type 1 diabetic patients with chronic kidney disease.  Eledon is developing tegoprubart as a tacrolimus-free immunosuppression regimen for preventing transplant rejection.

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Viking Therapeutics announced the completion of enrollment ahead of schedule in its Phase III VANQUISH-1 trial evaluating subcutaneous VK2735, a dual GLP-1/GIP receptor agonist, for treating obesity.  “We are excited to announce completion of enrollment in VANQUISH-1 ahead of schedule,” said Dr. Brian Lian, CEO of Viking.  VK2735 demonstrated up to 14.7% mean body weight reduction with no signs of plateau in the Phase II VENTURE study, along with encouraging safety and tolerability.

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Tandem Diabetes Care has launched its t:slim mobile application in Canada for both Android and iOS users, enabling patients to deliver boluses from compatible smartphones and wirelessly upload pump data to the cloud-based Tandem Source platform.

Read more: A new era in diabetes: five biotech companies moving past daily insulin injections

The emerging role of GLP-1s in inflammatory diseases by Garbrielle M. Grasso, Philip J. Mease, MD, Fatima Cody Stanford, MD/MPH, MPS, & Joel M. Gelfand, MD for Healio.com/dermatology, 9 December 2025.

About one in eight adults say they are taking a GLP-1 receptor agonist as a treatment for obesity, diabetes or another chronic condition, according to a new KFF Health Tracking Poll.

In this Beneath the Surface interview series (one of a 3-part series focused on the role of GLP-1s in inflammatory disease), Joel M. Gelfand, MD, MSCE, FAAD, the James J. Leyden Professor of Clinical Investigation and professor of dermatology and epidemiology at University of Pennsylvania’s Perelman School of Medicine and Healio Dermatology’s Chief Medical Editor, spoke with Fatima C. Stanford, MD, MPH, MPA, MBA, MACP, FAAP, FAHA, FAMWA, FTOS, an obesity medicine physician-scientist at Massachusetts General Hospital and associate professor of medicine and pediatrics at Harvard Medical School, and Philip Mease, MD, director of rheumatology research at the Swedish Medical Center/Providence St. Joseph Health and clinical professor at the University of Washington School of Medicine in Seattle, about the role of GLP-1s in inflammatory diseases.

Researchers have discovered that GLP-1s offer benefits across multiple specialties, including hepatology, nephrology, and cardiology. Emerging data also suggest these class benefits extend to dermatologic and rheumatologic conditions, such as psoriasis and rheumatoid arthritis.  “The list goes on and on as we look at where GLP-1 receptors are located throughout the body,” Stanford said. “We are going to continue to see use case scenarios for GLP-1 receptor agonists as we think about chronic inflammation in the body and how these can play a role in treating, not only cardiometabolic disease, but other inflammatory conditions as well.”

Addressing this inflammation with GLP-1s is becoming a growing practice, signaling a shift in inflammatory disease treatment, according to Mease.

Read more: The emerging role of GLP-1s in inflammatory diseases

MIT Researchers Develop Non-Invasive Glucose Monitor by HMENews.com, 30 December 2025.

A team of researchers at the Massachusetts Institute of Technology (MIT) has used Raman spectroscopy to develop a shoebox-sized device that can measure blood glucose levels without any needles. In tests on healthy volunteers, researchers found that the device’s measurements were similar to those of a commercial continuous glucose monitor that requires an implanted wire. “For a long time, the finger stick has been the standard method for measuring blood sugar, but nobody wants to prick their finger every day, multiple times a day,” says Jeon Woong Kang, an MIT research scientist.

Researchers recently published their work using Raman spectroscopy, a technique that reveals the chemical composition of tissues by shining near-infrared or visible light on them, in the Journal of Analytical Chemistry. While the device is too large to be used as a wearable sensor, researchers have since developed a smaller version, about the size of a cell phone, which they are now testing in a small clinical study of healthy and prediabetic volunteers. Next year, they plan to run a larger study working with a local hospital that will include people with diabetes. Researchers are also working on making the device even smaller – about the size of a watch. 

Read more: MIT researchers develop non-invasive glucose monitor