Category: Treatment

Published in the Journal of Clinical Investigation, researchers at University of Michigan Medical School looked for the mechanism behind sotagliflozin’s cardiovascular benefits. Sotagliflozin is FDA-approved as Inpefa for adults with heart failure, and for those with type 2 diabetes, chronic kidney disease and other cardiovascular risk factors.

Key findings:

• The problem: For people with type 2 diabetes, dangerous blood clots from overactive platelets are a major cause of heart attack and stroke.
• What makes sotagliflozin different: It is a dual inhibitor — it blocks both SGLT2 in the kidneys and SGLT1 in other organs. Most common drugs in this class, like empagliflozin (Jardiance) and dapagliflozin (Farxiga), only block SGLT2.
• Head-to-head lab tests: In blood samples from both healthy volunteers and people with type 2 diabetes, sotagliflozin limited excessive platelet activation. Empagliflozin had little to no effect.
• Anti-clotting effect: Sotagliflozin made platelets less likely to stick together. In mice with injured blood vessels, it reduced clot formation by about 60%, compared to 5-10% for empagliflozin.
• Why it works: Blocking SGLT1 in platelets alone reduced clotting by about 40% in mice, but didn’t fully explain sotagliflozin’s effect. A selective SGLT1 blocker, mizagliflozin, also didn’t replicate the full effect. Researchers think additional mechanisms — possibly involving SGLT1 in endothelial cells that line blood vessels — are involved.

What the researchers said:
Co-senior authors Dr. Michael Holinstat and Dr. Eugene Chen noted that blocking SGLT2 alone is not enough to inhibit platelet aggregation, and that sotagliflozin may offer protection against clots without increasing bleeding risk — a long-sought goal in clot prevention.

Co-author Dr. Bertram Pitt said sotagliflozin appears to be in a “sweet spot” because highly selective SGLT1 inhibitors can cause gastrointestinal issues.

Next steps and limitations:
The work was laboratory and animal research, not a clinical trial in patients. The authors say future studies should look at effects in conditions like chronic kidney disease and atrial fibrillation.

This is early mechanistic research. If you have questions about diabetes treatment and cardiovascular risk, it’s best to discuss them with your doctor or healthcare team.

Type 2 diabetes is rising worldwide, linked to obesity and long-term energy surplus. Insulin lowers blood sugar by pushing glucose into cells, but if that energy isn’t used, it gets stored as fat — so patients often keep gaining weight.

The new approach:
Instead of using drugs or engineered biological cells, researchers developed a fully inorganic, implantable electronic system. It was published in the journal Science.

How it works:

• The catalyst: Graphite felt covered with gold nanoclusters that are “dusted” with even smaller platinum particles. The surface looks like tiny desert roses under an electron microscope. It needs no cells, enzymes, or biological components, which could make manufacturing and regulatory approval easier. It showed good biocompatibility.
• What it does: Using a very low electrical voltage, it converts excess blood glucose into gluconate, which cannot be stored as fat and is excreted in urine.
• Closed-loop control: A standard continuous glucose sensor (like those worn on the arm) monitors glucose. If levels rise too high after a meal, it sends a Bluetooth signal to a smartphone/smartwatch, which wirelessly powers the implant at 13.56 MHz and activates the catalyst. It switches off automatically when glucose returns to target, reducing risk of low blood sugar.
• The implant: Contains the catalyst plus an electronic control unit in a 3D-printed casing, powered wirelessly.

What they tested:

1. In a lab reservoir with 5 litres of glucose solution — about the volume of human blood — it successfully converted glucose.
2. In diabetic mice for 6 weeks: blood sugar was precisely regulated, mice lost weight, and there was no evidence of tissue damage from electrical or heat effects.

What’s next:
No human testing yet. The team sees this as a paradigm shift from telling the body how to handle glucose (with drugs) to directly removing excess glucose with electronics. Because the components — sensors, wireless power, control electronics — already exist commercially, they plan to develop it into a medical device.

Researchers have identified elevated levels of a protein called Miro1 (Mitochondrial Rho GTPase1) in the skeletal muscle of people with Type 2 diabetes as a potential contributor to insulin resistance — and a possible future drug target.

What Miro1 does: Miro1 sits on the outer membrane of mitochondria (the cell’s energy producers). The team found that accumulation of Miro1 impairs muscle’s response to insulin.

Evidence across three levels:

1. In people: Miro1 levels were elevated in skeletal muscle of people with Type 2 diabetes.
2. In preclinical models: Removing Miro1 restored muscle insulin sensitivity, showing a causal effect.
3. With exercise: In a randomized controlled trial of people with obesity and Type 2 diabetes, aerobic exercise vs. standard medical care led to reductions in muscle Miro1, along with improved insulin sensitivity and muscle energy production.

Study details: Published in Nature Communications. Led by senior author Dr. John P. Kirwan — who did the work at LSU’s Pennington Biomedical Research Center and is now Executive Director of the OU Health Harold Hamm Diabetes Center at the University of Oklahoma. First author is Elizabeth Heintz, doctoral candidate at Pennington Biomedical; co-corresponding author is Christopher Axelrod, now also at Harold Hamm.

Significance and next steps: Insulin resistance in muscle is central to Type 2 diabetes but its molecular causes remain unclear. This work proposes Miro1 as a new therapeutic target and helps explain why exercise is effective. The authors note more research is needed to determine if targeting Miro1 can lead to new treatments.

This trial found that continuous glucose monitors (CGMs) meaning small sensors worn on the body that track glucose all day and night, significantly improved blood sugar control in type 2 diabetes patients who do not use insulin.

What the study did:

• Largest trial of its kind for this population: 283 adults across 22 US primary care practices, followed for 26 weeks
• Published in the New England Journal of Medicine
• First large-scale, multicenter randomized controlled trial to focus only on patients treated in primary care, where most Americans with type 2 diabetes receive care

Key results:

• Time in range: CGM users spent about 5 more hours per day in their target blood sugar range compared with routine care
• A1c (a measure of average blood sugar over about 3 months): CGM group improved by 0.9 percentage points more than the control group. The authors note this greatly exceeds what is generally considered clinically meaningful
• A1c goal: Nearly twice as many CGM users reached an A1c below 7%, a common treatment goal

Why it matters:
An estimated 20 million US adults have type 2 diabetes and do not take insulin, and many do not reach glycemic targets, which over time raises risk for heart disease, kidney disease, and vision loss.

Currently, American Diabetes Association guidelines cite Level A evidence, the highest rating, for CGM use in people who use insulin, but only Level C evidence, reflecting limited research, for people who do not use insulin. The authors hope this trial provides robust evidence to strengthen guidelines and expand insurance coverage.

For now, they suggest people with type 2 diabetes not using insulin discuss CGM use with their primary care provider.

A new study led by UCLA Health, published in JAMA Network Open. Analyzed 2019 national health records of 587,000 Medicare Advantage patients:

Main Findings:

• Overall adherence to diabetes medications was less than 60%. Patients were considered “adherent” if at least 80% of days were covered.
• Black and Hispanic patients were less likely than White patients to adhere to medication protocols.
• For metformin specifically, Black patients had significantly lower adherence than White patients — 46% vs. 56.5% — despite metformin being low-cost and widely available.

Medications Evaluated: metformin, insulin, and a combined group of SGLT2 inhibitors and GLP-1 RAs.

Role of Financial Assistance:

• Assistance programs — Medicaid and Medicare’s Part D Low-Income Subsidy — significantly helped reduce treatment gaps.
• The effect was most pronounced for high-cost treatments like insulin and newer drugs such as SGLT2 inhibitors and GLP-1 RAs.

Author Statements:
Lead author Dr. Utibe R. Essien, associate professor-in-residence at UCLA’s David Geffen School of Medicine, said consistent medication use is critical for preventing long-term complications, and that health plan rules and out-of-pocket costs strongly affect adherence. He said clinicians can help connect patients with financial support programs, and noted that non-financial factors — such as pharmacy closures, dosing complexity, side effects, or personal beliefs about treatment — may explain disparities in low-cost drugs and require further research.

New research to be presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan (Sept 28 – Oct 2) — from Prof. Dominic Ehrmann, Research Institute Diabetes Academy Mergentheim, Germany, and colleagues.

Goal of the study:
To understand how day-to-day blood sugar patterns affect quality of life in people with diabetes. The PRO-MENTAL study, funded by the German Centre for Diabetes Research (DZD), looked at whether CGM data from one day predicts quality of life the next day.

How it was done:

• 400 people with diabetes: 72% type 1, 28% type 2, 55% female, average age 47, average HbA1c 7.6%
• 14 consecutive days of monitoring
• Quality of life was rated daily using ecological momentary assessment (EMA) based on the WHO-5 questionnaire, which asks about feeling cheerful, calm, active, rested, and interested in daily life. Sleep quality, perceived stress, mood and energy (0-10 scale) were also recorded daily.
• CGM parameters analyzed: time below range (<70 mg/dL), time above range (>180 mg/dL), time in normal range (70-140 mg/dL), and glucose variability.
• Models adjusted for age, sex, diabetes type, and previous-day quality of life.

Key findings:

1. More time in the normal range (70-140 mg/dL) on one day was associated with better quality of life the next day.
2. Higher glucose variability — while still within safe limits — on one day was also associated with better quality of life the next day.
3. Time above range and time below range showed no significant link to next-day quality of life.
4. Better sleep quality the previous night and higher energy levels the previous day were also linked to better next-day quality of life.
5. Same-day glucose parameters were not associated with same-day quality of life.

Authors’ interpretation:
The researchers suggest that while good blood sugar control is important for well-being, trying to minimise fluctuations too strictly — even when staying within safe limits — may carry a burden that reduces enjoyment. The constant effort and restriction needed to keep glucose completely flat could prevent people from engaging in activities they enjoy.

The study does not suggest that looser control is better, but that the psychological and practical burden of very strict control may affect day-to-day quality of life.

This is conference research that has not yet been through full peer-reviewed publication, so findings should be considered preliminary.

A class of medicines used for type 2 diabetes that also reduces risk of heart and kidney disease. They carry a rare but serious side effect: ketoacidosis — where lack of insulin leads to high ketone production, disrupting the body’s acid-base balance and potentially becoming life-threatening.

What the study did:
Published in The Lancet Diabetes & Endocrinology, researchers analyzed national health registry data from Sweden, Denmark and Norway. It included more than 280,000 patients with type 2 diabetes treated with SGLT2 inhibitors, looking at how often ketoacidosis occurred and what factors increased risk. Collaboration with Statens Serum Institut (Denmark) and NTNU (Norway).

Key findings on who is at higher risk:

• Highest risk factors: history of previous ketoacidosis, high blood glucose levels, low body weight or signs of malnutrition
• Also linked to higher risk: previous episodes of hypoglycaemia (low blood sugar)
• Most common trigger: infection was the most common triggering or co-occurring event when ketoacidosis happened
• Other acute conditions were more common in affected patients, including kidney impairment, stroke, and major surgery

Timing of risk:
Previous studies focused on the early months of treatment. This study found risk is highest in the first few months, but remains elevated throughout the entire time a patient is on the medication.

What it means for clinical care:
Lead author Peter Ueda, Assistant Professor at Department of Medicine, Solna, Karolinska Institutet, said the goal is not to avoid treatment — SGLT2 inhibitors benefit many patients — but to better identify high-risk patients and use the drugs more safely.

Researchers hope the findings help clinicians with treatment decisions and with guidance on when to temporarily pause the medication, for example during acute illness or before surgery.

Next steps are to study in more detail the patients who do develop ketoacidosis on treatment, and to investigate other rare but serious side effects of modern diabetes medicines.

Researchers at UC Berkeley have identified a compound that could treat obesity, diabetes, and fatty liver disease differently than current GLP-1 drugs like Ozempic, Wegovy, Mounjaro and Zepbound.

How it works:

• GLP-1s work by reducing appetite and food intake, which can cause side effects like nausea, nutritional deficiencies, and muscle loss.
• The new compound, 5-tetradecyloxy-2-furoic acid (TOFA), works on the other side of the energy equation: it increases energy expenditure.
• TOFA has a dual mechanism. It is an ACC inhibitor that blocks production of lipids like cholesterol and triglycerides, AND it activates cellular receptors PPARα and PPARδ that turn on genes to help cells take up fat and burn it for energy.

Results in mice, published in Science Advances:

• Cells burned up to 18% more energy with no change in food intake, physical activity, or body temperature.
• Obese mice lost weight from fat with no significant loss of lean muscle mass.
• Improved insulin sensitivity, glucose control, lowered triglycerides, and improved features of fatty liver disease.
• Unlike other ACC inhibitors that reached mid-stage clinical trials, TOFA did not raise triglycerides, a major heart risk that has prevented approval of others in this class.

Combination potential:

• When researchers gave mice two separate drugs to replicate TOFA’s two actions, it was less effective than TOFA alone.
• When combined with GLP-1 drugs semaglutide and tirzepatide, TOFA worked additively or synergistically, leading to greater improvements in weight, glucose, insulin, and triglycerides than either alone. Researchers view it as complementary, not a replacement.

TOFA was first discovered in the 1970s. The study was led by senior author Anders Näär, professor of metabolic biology and nutrition at UC Berkeley, and first author Justin Y. Lee.

A new review published in Genes & Diseases identifies trained immunity — a long-lasting adaptation of the innate immune system — as a key mechanism in diabetes and its complications.

Here is a summary of the press release:

What is trained immunity?
It’s a form of immune memory where innate immune cells like monocytes and macrophages undergo lasting changes after exposure to metabolic stress or inflammation. They become primed to react more aggressively to future triggers, creating a state of chronic, low-grade inflammation that can persist even after blood sugar normalizes.

What triggers it in diabetes?
The review found that common diabetes-related factors can activate these pathways, including:

• Hyperglycemia (high blood sugar)
• Obesity
• Lipid abnormalities
• Changes in the gut microbiome

Why it matters for disease progression:
This sustained inflammatory response can:

• Promote insulin resistance
• Impair insulin-producing beta cell function
• Accelerate tissue damage

Beyond diabetes itself, trained immunity may help explain major complications, including atherosclerosis and cardiovascular disease, diabetic kidney disease, delayed wound healing, tissue fibrosis, and vascular dysfunction.

New treatment opportunities:
The authors suggest future therapies should target the immune mechanism itself, not just blood glucose. Promising directions highlighted include:

• Targeting inflammatory pathways like the NLRP3 inflammasome
• Modifying cellular metabolism (immunometabolism)
• Improving gut microbial balance through diet and microbiome-focused therapies
• Exploring vaccination strategies that reprogram immune responses

The overall shift is from viewing diabetes as purely a metabolic disorder to understanding it as a disease with a persistent innate immune component — opening new avenues for prevention and treatment of its long-term complications.

A new mouse study published this week in the Journal of Virology suggests that GLP-1 agonists — drugs commonly used for type 2 diabetes and weight loss — could help prevent pulmonary fibrosis in diabetic patients with Long COVID.

Key findings:

• The problem: People with type 2 diabetes have ∼4x higher risk of severe Long COVID symptoms than non-diabetics. Pulmonary fibrosis, a severe Long COVID condition where lung tissue becomes scarred and thickened, is driven by immune cells called macrophagesAmerican Society for Microbiology.
• The research: Led by virologist Runhong Zhou, Ph.D., at the University of Hong Kong, researchers compared blood samples from COVID-19 patients with and without diabetes months after hospitalization. Diabetic patients showed increased monocyte activity and genetic pathways linked to fibrosis.
• The mouse experiments: Mice with diabetes and SARS-CoV-2 infection developed overactive fibrosis-related genes. When treated with GLP-1 agonists, those genes normalized and macrophages were “reprogrammed,” leading to reduced lung scarring compared to untreated mice.
• Why GLP-1s?: The GLP-1 receptor is highly expressed in lung cells, and earlier lab work hinted at anti-inflammatory effects against pneumonia-related fibrosis. This is the first test in animal models after severe COVID-19 infection.

Caveats: Zhou notes the results are preliminary and only involved a small number of mice. But the team sees it as proof of concept worth further investigation, especially since Long COVID continues to affect many people, particularly the elderly.

The study was announced by the American Society for Microbiology on 9 July 2026.

A review published 23 June 2026 in Diabetes Care from the Immunology of Diabetes research group at the Germans Trias i Pujol Research Institute (IGTP) examines whether physical activity could serve as a complementary strategy for type 1 diabetes beyond blood sugar management.

Key points from the review:

• Focus: Type 1 diabetes is autoimmune — the immune system destroys insulin-producing beta cells. The paper looks at exercise’s potential to influence that immune process.
• Preclinical evidence: In animal models, exercise may reduce immune cell infiltration into pancreatic islets, protect beta cells, and increase anti-inflammatory mediators.
• Human data: Still limited, but some studies link physical activity to longer partial remission periods and anti-inflammatory immune profiles.
• What it isn’t: Authors stress exercise does not cure type 1 diabetes or replace insulin. It’s a potential low-risk, patient-centered complement.

Next steps called for:

• More clinical studies to identify optimal exercise type, intensity, duration, and timing
• Development of immunological markers to measure impact
• Integration with emerging early detection and immunotherapy strategies

Goal: Understand how exercise affects autoimmunity to potentially help restore immune tolerance, preserve remaining beta cells, and reduce complications.

First author Daniel A. Cook notes that specific studies are needed to clarify mechanisms and position exercise as both a complement to insulin therapy and a preconditioning strategy for immunotherapy.

Researchers at the University of Zurich, University Hospital Zurich, and University of Pisa found that targeting epigenetic “readers” in perivascular fat — the fat layer surrounding blood vessels — can reduce inflammation and improve vessel health in both mice and human tissue. This approach may help prevent vascular damage in people with obesity and type 2 diabetes.

Why perivascular fat matters
Perivascular fat actively communicates with vessel walls to control relaxation and inflammation. In obesity and metabolic disease, this fat becomes inflamed, stores lipids abnormally, and releases molecules that stiffen vessels and impair function, contributing to early vascular disease, heart attacks, and strokes.

What the study did
Instead of targeting single downstream molecules, the team used BET protein inhibitors — epigenetic drugs that modulate how genes are “read” — to retune the entire gene activity program in perivascular fat cells.

Results

• In lab tests on mice and human tissue, the drugs shifted fat cells away from an inflammatory profile.
• Blood vessels surrounded by reprogrammed fat relaxed more easily and showed fewer signs of damage.
• A key driver identified was the enzyme hexokinase 2, which regulates sugar metabolism. Overactive hexokinase 2 makes fat cells store more fat and release inflammatory signals that harm vessels. Lowering its activity, either via epigenetic modulation or direct inhibition, blunted inflammation and restored normal vessel function in samples.

Potential impact
Led by UZH cardiologist Francesco Paneni, the study suggests epigenetic therapies could complement current treatments for blood pressure, cholesterol, and blood sugar. Rather than only managing downstream risk factors after damage starts, this approach aims to reprogram the tissue processes that cause vascular damage, potentially reducing progression to heart attack or stroke in obesity and metabolic disease.

Published June 1, 2026 in Proceedings of the National Academy of Sciences by researchers at Sanford Burnham Prebys Medical Discovery Institute and the University of Michigan. Senior author: Randal J. Kaufman, PhD.

The Core Problem
In healthy beta cells, proteins must fold into precise 3D shapes to work — like origami. As prediabetes progresses to diabetes, proinsulin, the precursor to insulin, often misfolds. Misfolded proinsulin builds up, stresses beta cells, and contributes to their failure to meet insulin demand.

What They Studied
The team investigated how beta cells manage proinsulin folding, focusing on the chaperone protein binding immunoglobulin protein (BiP) and its partner proteins. To track BiP, they engineered mice with a 3xFLAG-tagged version of BiP in beta cells.

Key Findings

1. p58IPK is a critical helper: Removing p58IPK, a BiP cochaperone, caused misfolded proinsulin to accumulate in cell lines. Mice lacking p58IPK made less proinsulin and insulin.
2. p58IPK can’t replace BiP, but helps it: Reintroducing p58IPK restored proper proinsulin folding and trafficking, but only when BiP was also present. Overexpressing BiP without p58IPK gave only modest improvements.
3. It’s a team effort: “Like a single tennis player trying to play a doubles match, BiP cannot just go it alone,” said lead author Insook Jang, PhD.
4. Other players involved: Additional partner proteins also help with proinsulin folding and quality control, but their exact roles need more study.

Why It Matters
Current diabetes drugs mainly help tissues absorb sugar or boost insulin release — they don’t fix the root problem of beta cell stress from misfolded proteins. This work shows proinsulin folding is vulnerable to the same cellular stresses that drive type 2 diabetes.

If researchers can figure out how to support BiP and its cochaperones like p58IPK, they may develop treatments that promote proper proinsulin folding, protect beta cells, and intervene earlier in diabetes progression.

A new study presented at the 28th European Congress of Endocrinology (ECE 2026) in Prague, 9–12 May, found that dementia risk varies by diabetes type and treatment, with insulin users facing the greatest risk.

Key findings:

• Researchers from Kyung Hee University Hospital at Gangdong and Samsung Medical Center tracked over 1.3 million South Korean adults aged 40+ without dementia from 2013–2024.
• Compared to people without diabetes:
  • Type 2 diabetes on oral meds: ∼1.3x higher risk of dementia
  • Type 2 diabetes using insulin: 2.1x higher risk
  • Type 1 diabetes: 2.4x higher risk
• The pattern held for both Alzheimer’s disease and vascular dementia.

Why it matters:
Lead author Prof. Ji Eun Jun noted this suggests “not all types of diabetes carry the same risk” and that people with insulin-dependent treatment “may be particularly vulnerable to cognitive decline”. Recurrent hypoglycemia and greater glucose fluctuations in insulin-treated patients may partly explain the link.

Implications:
The authors recommend recognizing diabetes as a brain health risk factor, not just metabolic. Prevention strategies like earlier cognitive monitoring and improving long-term glucose stability, such as continuous glucose monitoring, should be considered in routine diabetes care.

The study was published in Diabetes, Obesity and Metabolism.

The FreeDM2 clinical trial found that real-time continuous glucose monitoring (CGM) significantly improves blood sugar control in adults with type 2 diabetes who use basal insulin, compared to traditional finger-prick testing.

Study Details

• Published in: The Lancet Diabetes and Endocrinology on 23 April 2026. Findings also presented at the Diabetes UK Professional Conference in Liverpool.
• Led by: Dr Emma Wilmot, University of Nottingham/University Hospitals of Derby and Burton NHS Foundation Trust, and Dr Lala Leelarathna, Imperial College London/Imperial College Healthcare NHS Trust.
• Participants: 303 adults with type 2 diabetes on basal insulin, randomly assigned to either real-time CGM or finger-prick monitoring.
• Duration: 16-week self-management period, followed by 16 weeks of clinician-supported care.

Results

• CGM users had significantly greater reductions in HbA1c (the key measure of long-term blood glucose) at both 16 and 32 weeks.
• Benefits were seen in both the self-management phase and the clinician-guided phase.
• In phase 1, improvements occurred without new medications, suggesting participants used CGM data to make meaningful lifestyle changes.

Context

• Type 2 diabetes makes up ∼90% of diabetes cases globally. High blood glucose increases risk of blindness, amputations, heart disease, and early death.
• CGM uses a small arm sensor that sends glucose readings to a phone/reader, with alarms for high/low levels. It’s less painful than finger-pricks and gives 24/7 data.
• While CGM is standard care for type 1 diabetes in the UK, its role in type 2 has been uncertain, limiting access.

A small peer-reviewed study published in the latest Journal of the Endocrine Society found that a ketogenic diet may help improve beta-cell function in people with type 2 diabetes, potentially aiding diabetes reversal.

Key findings

• Study design: 51 adults with type 2 diabetes, ages 55-62, 71% female, were assigned to either a ketogenic diet or a low-fat diet for 3 months. Both diets were designed to be weight-maintaining.
• What improved: The ketogenic diet group showed greater improvement in beta-cell function compared to the low-fat group. Beta cells in the pancreas secrete insulin to control blood sugar, and they often underperform in type 2 diabetes.
• How it was measured: Researchers tracked the proinsulin-to-C-peptide ratio, a biomarker of beta-cell stress. This ratio decreased more in the keto group, indicating reduced stress on the pancreas and better insulin secretion ability.
• Weight loss: Both groups lost a modest amount of weight on average, but the keto diet’s benefits to beta-cell function occurred independently of substantial weight loss.

Why it matters

• Current gap: According to lead author Marian Yurchishin, M.S., of the University of Alabama at Birmingham, “Other than bariatric surgery or large-volume intentional weight loss, interventions for improving beta-cell function in type 2 diabetes do not currently exist.”
• Mechanism: A ketogenic diet is high-fat, low-carb and shifts metabolism to burn fat instead of storing it. The authors suggest this reduces stress on the pancreas and improves beta-cells’ ability to secrete insulin.

Study details

• Authors: Marian Yurchishin, Amanda Finn, Lauren Fowler, and Barbara Gower of UAB; Sara Vere-Whiting of University of Glasgow.
• Funding: National Institute of Diabetes and Digestive and Kidney Diseases, UAB Nutrition Obesity Research Center, UAB Diabetes Research Center, and National Heart, Lung, and Blood Institute.
• Context: The study was small and focused on patients with early type 2 diabetes. More research would be needed to confirm long-term effects and applicability to broader populations.

Researchers at Karolinska Institutet and KTH Royal Institute of Technology in Sweden published a peer-reviewed study in Stem Cell Reports detailing an improved method to create insulin-producing cells from human stem cells.

Key findings

• More reliable production: The new method consistently generates high-quality, mature insulin-producing cells from multiple human stem cell lines, addressing past issues where methods produced mixed, immature cell populations.
• Better function in lab tests: In vitro, the cells secreted insulin and showed strong glucose responsiveness.
• Reversed diabetes in mice: When transplanted into the anterior chamber of the eye of diabetic mice, the cells gradually matured and restored blood sugar regulation for several months.

Why it matters

• Patient-specific potential: Works across different stem cell lines, which could enable personalized cell therapies with reduced immune rejection, per lead authors Per-Olof Berggren and Siqin Wu.
• Solves prior barriers: By refining culture steps and letting cells form 3D clusters themselves, the process eliminates many unwanted cell types and improves glucose responsiveness — two major hurdles in past trials, according to Fredrik Lanner.
• Clinical next steps: The team aims to move toward clinical translation for treating type 1 diabetes.

Context & notes

• Type 1 diabetes results from immune destruction of pancreatic insulin-producing cells, leaving patients unable to regulate blood sugar.
• The eye chamber transplant technique allows minimally invasive monitoring of cell development over time.
• Funded by the Swedish Research Council, Novo Nordisk Foundation, ERC, and others. Some researchers report industry links, including patents and employment at Spiber Technologies AB and Biocrine AB. Karolinska Institutet

A new study led by researchers at Stanford Medicine suggests that about 1 in 10 people may have a genetic resistance to GLP-1 diabetes drugs, such as Ozempic and Wegovy, when these medications are used to control blood sugar in people with Type 2 Diabetes.

The study found that certain variants in the PAM gene, carried by roughly 10% of the population, are linked to a phenomenon researchers call GLP-1 resistance. People with these variants have higher levels of the GLP-1 hormone, but the hormone is less biologically effective, meaning it does not lower blood sugar as well as expected. This was unexpected, since researchers initially thought these individuals would have lower hormone levels.

After experiments in both humans and mice, the researchers confirmed that this resistance is real. In mouse models, GLP-1 activity was reduced despite normal receptor function, suggesting that the problem likely occurs further downstream in the signaling pathway, though the exact mechanism remains unknown.

Analysis of clinical trial data involving more than 1,100 participants showed that people with PAM variants were less likely to reach target HbA1c blood sugar levels after six months of treatment with GLP-1 receptor agonists. Importantly, this reduced response appeared to be specific to GLP-1 drugs, as responses to other diabetes medications like metformin were unaffected.

The findings could be an important step toward precision medicine, allowing doctors to use genetic testing to predict which patients are less likely to benefit from GLP-1 therapies and choose better treatments earlier. Researchers also note that longer-acting GLP-1 drugs may help overcome this resistance, though more research is needed, especially regarding effects on weight loss