The Forgotten Insulin Sensitizer: Revisiting Pioglitazone for Metabolically Unhealthy Non-Obese (MUNO) Indians with T2DM

MUNO Indian Phenotype: A Silent High-Risk Candidate

The Metabolically Unhealthy Non-Obese (MUNO) phenotype is a silent but high-risk profile, especially common among South Asians. Despite a normal BMI, these individuals have markedly higher visceral and liver fat, increased carotid intima-media thickness (CIMT), and reduced insulin sensitivity and secretion, which significantly elevates the risk of T2D and CVD. (1) An Indian study (n= 2,560) found that 97.1% of normal-BMI adults were metabolically unhealthy, highlighting the urgency of early identification and addressing the clinical needs of MUNO. (2)

Pioglitazone: Addressing the Pathophysiological Needs Associated with MUNO

Pioglitazone enhances insulin sensitivity by activating PPAR-γ and AMPK pathways, thereby promoting peripheral glucose uptake, improving hepatic insulin action, and reducing endogenous glucose production. It also improves adipose tissue function, lowers triglycerides, raises HDL, and shifts fat from visceral to subcutaneous depots—mechanistically aligning with the core metabolic defects seen in the MUNO phenotype.(3,4)

Clinical Evidence with Pioglitazone: Glycemic and Beyond-Glycemic Benefits

Effect on HbA1c, Lipid & Insulin Function: A 23-week, multicenter, double-blind RCT enrolled 197 patients with T2DM (HbA1c ≥8%, FPG >140 mg/dL, C-peptide >1 ng/mL) to assess the efficacy and safety of pioglitazone vs. placebo. Pioglitazone significantly reduced HbA1c (−1.37%, p=0.0001), FPG (−57.5 mg/dL), HOMA-IR (−12.4%), and triglycerides (−16.6%), while increasing HDL-C (+12.6%) and β-cell function [+47.7%]. (5)

Effect on Progression of NAFLD: In an 18-month randomized, double-blind, placebo-controlled trial (n=101) with biopsy-proven NASH and prediabetes or T2DM, pioglitazone reduced the NAFLD activity score—defined as a ≥2-point reduction in at least two histologic categories without worsening of fibrosis (primary endpoint)—in 58% of patients (p<0.001) and achieved NASH resolution in 51% of the cases. It also improved fibrosis score (−0.5) and reduced hepatic fat by ~63% (absolute −12%). Benefits persisted through 36 months. (6)

Effect on Cardiovascular Risk: In the IRIS trial, 3,876 patients without diabetes but with insulin resistance and a recent ischemic stroke or TIA were randomized to receive pioglitazone or placebo over a median of 4.8 years. Pioglitazone reduced the risk of stroke or myocardial infarction by 24% (HR 0.76, p=0.007). It also achieved a 52% relative risk reduction in new-onset diabetes [HR 0.48, p<0.001]. (7)

Safety of Pioglitazone

The above studies, which demonstrated the clinical benefits of pioglitazone, also provide important insights into its safety profile. While higher rates of weight gain, edema, and fractures were observed compared to placebo, the absolute risk remained low, and no significant increase in heart failure or cancer risk was reported.Long-term use revealed no new safety signals or major drug-related adverse events, supporting its acceptable safety profile in appropriately selected patients. (5,6,7)

Dosing considerations: For adults and elderly patients, initiate treatment at 15-30 mg orally once daily, with possible 15 mg incremental increases based on therapeutic response, not exceeding a maximum daily dose of 45 mg.

Contraindications: Pioglitazone is contraindicated in patients with hypersensitivity to the drug, diabetic ketoacidosis, heart failure (NYHA Class III-IV in the US, any class in Canada), fluid overload, active or previous bladder cancer, high fracture risk, active liver disease with elevated transaminases, and pregnancy. It should not be initiated in patients with hypoglycemia requiring frequent monitoring, and is considered potentially inappropriate for elderly patients with heart or kidney failure.(8) Its cardiovascular benefits must be balanced against fracture risk, especially in postmenopausal women. (9) Mild anemia may occur due to hemodilution (10), and fluid retention may worsen or exacerbate existing or developing heart failure. (11)

Case-Based Scenarios: When to Consider?

A 41-year-old man with a normal BMI (22.2 kg/m2) presents with newly diagnosed T2DM. His fasting insulin is elevated at 22 µIU/mL, and HOMA-IR is calculated at 5.9, indicating significant insulin resistance. An abdominal ultrasound shows grade I hepatic steatosis consistent with mild fatty liver. With no hypertension or CVD, his profile reflects early metabolic dysfunction. Pioglitazone may be considered in this case to improve insulin sensitivity and prevent the progression of MASLD.

MASLD & T2DM: Guidelines Spotlight

  • Indian Diabetologists’ Consensus on MASLD (2025): Suggested considering pioglitazone as an anti-hyperglycemic agent in patients with T2DM and MASLD, especially when individualized therapy is needed or lifestyle interventions are insufficient, due to its potential hepatic benefits. (12)
  • Global MASH Council Consensus (2025): Suggests considering pioglitazone for type 2 diabetes in individuals with or without MASH, but not as a MASH-targeted therapy. (13)
  • ADA (2025): Recommends pioglitazone, a GLP-1 RA, or dual GIP/GLP-1 RA for glycemic control in adults with T2DM and biopsy-confirmed MASH or high fibrosis risk, given their potential benefits on MASH. (14)
  • AASLD (2023): States that pioglitazone improves NASH and may be considered for patients with NASH in the context of T2DM. (15)
  • AACE (2023): Suggest considering pioglitazone in T2D patients with comorbidities such as stroke, NAFLD, or prediabetes. Pioglitazone may also help improve triglyceride levels and reduce the risk of recurrent stroke in those with prior TIA or stroke. (16)
  • RSSDI (2022): Recommends pioglitazone for secondary prevention in patients with stroke or TIA, and also for diabetes management in elderly individuals. (17)

Key Takeaways

  • Nearly 97% of normal-BMI Indian adults are metabolically unhealthy, underlining the need to identify and manage the MUNO T2D phenotype early.
  • Pioglitazone directly targets insulin resistance, adipose redistribution, and hepatic steatosis, making it a mechanistically rational therapy for MUNO patients.
  • Evidence supports both glycemic (HbA1c, HOMA-IR) and non-glycemic (NASH resolution, CVD risk reduction) benefits.
  • Supported by global and Indian guidelines, like the Indian Diabetologists’ Consensus (2025), Global MASH Council (2025), ADA (2025), AASLD (2023), AACE (2023), and RSSDI (2022), pioglitazone remains a relevant but underutilized option in specific patient profiles (T2DM, MASLD, and stroke-risk patients.)
  • Pioglitazone-based FDCs offer a practical approach for addressing the silent metabolic dysfunction in MUNO, especially when dual therapy fails to target insulin resistance effectively.

References:

1. Stefan, Norbert et al. “Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans.” Cell metabolism vol. 26,2 (2017): 292-300. doi:10.1016/j.cmet.2017.07.008

2. Sivanantham, Parthibane et al. “High prevalence of abdominal obesities and metabolically unhealthy individuals in a highly urbanized district of India: findings of a cross-sectional survey in Puducherry.” Family practice vol. 40,2 (2023): 282-289. doi:10.1093/fampra/cmac082

3. Coletta, D K et al. “Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial.” Diabetologia vol. 52,4 (2009): 723-32. doi:10.1007/s00125-008-1256-9

4. Sourij H, Wascher TC. Pioglitazone in the management of Type 2 diabetes and beyond. Drugs. 2010;70(8):925–954.

5. Rosenblatt, S et al. “The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus.” Coronary artery disease vol. 12,5 (2001): 413-23. doi:10.1097/00019501-200108000-00011

6. Cusi, Kenneth et al. “Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial.” Annals of internal medicine vol. 165,5 (2016): 305-15. doi:10.7326/M15-1774

7. Kernan, Walter N et al. “Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.” The New England journal of medicine vol. 374,14 (2016): 1321-31. doi:10.1056/NEJMoa1506930

8. Singh G, Can AS, Correa R. Pioglitazone. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544287/

9. Azhari, Hala F, and Jesse Dawson. “Clinical implications of fracture severity risk with pioglitazone: a systematic review and meta-analysis of clinical randomized trials.” Frontiers in pharmacology vol. 16 1357309. 6 Mar. 2025, doi:10.3389/fphar.2025.1357309

10. Antoniadou, Christina et al. “Anemia in diabetes mellitus: Pathogenetic aspects and the value of early erythropoietin therapy.” Metabolism open vol. 25 100344. 4 Jan. 2025, doi:10.1016/j.metop.2024.100344

11. Kavanagh, Kylie et al. “Fluid compartmental shifts with efficacious pioglitazone therapy in overweight monkeys: implications for peroxisome proliferator-activated receptor-gamma agonist use in prediabetes.” Metabolism: clinical and experimental vol. 59,6 (2010): 914-20. doi:10.1016/j.metabol.2010.02.010

12. Zargar, Abdul Hamid et al. “Management of metabolic dysfunction-associated steatotic liver disease (MASLD)-An expert consensus statement from Indian diabetologists’ perspective.” Diabetes, obesity & metabolism vol. 27 Suppl 4,Suppl 4 (2025): 3-20. doi:10.1111/dom.16496

13. Younossi, Zobair M et al. “Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis.” Gastroenterology, S0016-5085(25)00632-8. 11 Apr. 2025, doi:10.1053/j.gastro.2025.02.044

14. American Diabetes Association Professional Practice Committee; 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025. Diabetes Care 1 January 2025; 48 (Supplement_1): S181–S206. https://doi.org/10.2337/dc25-S009

15. Rinella, Mary E et al. “AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.” Hepatology (Baltimore, Md.) vol. 77,5 (2023): 1797-1835. doi:10.1097/HEP.0000000000000323

16. Samson, Susan L et al. “American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm – 2023 Update.” Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists vol. 29,5 (2023): 305-340. doi:10.1016/j.eprac.2023.02.001

17. RSSDI (2022). RSSDI Clinical Practice Recommendations 2022: Summary Document for Training. Research Society for the Study of Diabetes in India (RSSDI).

Abbreviations: MUNO: Metabolically Unhealthy Non-Obese, T2DM: Type 2 Diabetes Mellitus, CVD: Cardiovascular Disease, PPAR-γ: Peroxisome Proliferator-Activated Receptor Gamma, AMPK: AMP-Activated Protein Kinase, HbA1c: Hemoglobin A1c, FPG: Fasting Plasma Glucose, HOMA-IR: Homeostasis Model Assessment of Insulin Resistance, HDL-C: High-Density Lipoprotein Cholesterol, NAFLD: Non-Alcoholic Fatty Liver Disease, NASH: Non-Alcoholic Steatohepatitis, MASLD: Metabolic Dysfunction-Associated Steatotic Liver Disease, MACCE: Major Adverse Cardiovascular and Cerebrovascular Events, CKD: Chronic Kidney Disease, ESRD: End-Stage Renal Disease, TIA: Transient Ischemic Attack, RCT: Randomized Controlled Trial, ADA: American Diabetes Association, AASLD: American Association for the Study of Liver Diseases, AACE: American Association of Clinical Endocrinology, RSSDI: Research Society for the Study of Diabetes in India

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Shingrix Vaccine Cuts Risk of Herpes Zoster Ophthalmicus, Heart Attack, and Stroke in Adults 50+: Study

A new study published in the journal of Clinical Infectious Diseases showed that in addition to reducing the incidence of herpes zoster ophthalmicus (HZO) by 72.9%, the recombinant herpes zoster vaccine (Shingrix) was associated with a decreased risk of hospitalization for acute myocardial infarction (MI) and stroke in patients 50 years of age and older.

A prevalent illness in older persons, herpes zoster (HZ) is brought on by the reactivation of the latent varicella zoster virus and can result in serious morbidity and a reduced quality of life. Herpes zoster ophthalmicus, one of its most severe forms, can cause long-term eye problems and vision loss. The adjuvanted recombinant zoster vaccine (RZV), which provides strong and long-lasting protection against HZ across age groups, has revolutionized preventative measures. 

Thereby, to optimize preventive treatment and guide vaccination programs for older populations at increased risk for cardiovascular and infectious problems, it is imperative to comprehend these protective benefits. This study assessed the relationship between recombinant zoster vaccine and risk for hospitalized stroke, hospitalized acute myocardial infarction (AMI), and hospitalized HZO in adults aged ≥50 years (YoA).

Using sex, age, race/ethnicity, and index date (date of second dose among vaccinated; date of unvaccinated match assigned same date), this research matched adults ≥50 YoA who received 2 doses of RZV 4 weeks–6 months apart between 01 April 2018 and 31 December 2020 1:4 to RZV-unvaccinated individuals.

The follow-up period began on the index date and terminated on December 31, 2022, or upon receiving the zoster vaccination, membership termination, or death, whichever occurred first. ICD-10 codes were used to identify inpatient AMI and stroke, whereas natural language analysis of clinical notes was used to identify HZO. 

The median age was 68 years (range: 50, 108), 59.0% of the 102,766 2-dose RZV-vaccinated and 411,064 unvaccinated people were female, and 57.1% were non-Hispanic White.

When comparing RZV-vaccinated and unvaccinated persons, the aHRs (95% CI) for inpatient stroke, hospitalized AMI, and HZO were 0.575 (0.533, 0.619), 0.720 (0.588, 0.881), and 0.271 (95% CI: 0.222, 0.330), respectively. 72.9% (67.0%, 77.8%) was the adjusted RZV efficacy against HZO. Overall, two RZV dosages were linked to a decreased incidence of HZO, AMI, and stroke in persons aged ≥50 years.

Source:

Rayens, E., Sy, L. S., Qian, L., Wu, J., Ackerson, B. K., Luo, Y., Zheng, C., Cheng, Y., Vega Daily, L. I., Song, J., Takhar, H. S., Ku, J. H., Cohen, R. A., Yun, H., Oraichi, D., Seifert, H., & Tseng, H.-F. (2025). Adjuvanted recombinant zoster vaccine is effective against herpes zoster ophthalmicus, and is associated with lower risk of acute myocardial infarction and stroke in adults aged ≥50 years. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. https://doi.org/10.1093/cid/ciaf440

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GLP-1RA Use May Lower Overall Cancer Risk but Increase Kidney Cancer Risk in Obese Patients: JAMA

USA: A new study published in JAMA Oncology has revealed that glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes management and weight loss, may have an impact on cancer risk among adults with obesity.

The research, led by Hao Dai and colleagues from the Department of Biostatistics and Health Data Science, Indiana University School of Medicine, explored the association between GLP-1RA use and the likelihood of developing cancer.
GLP-1RAs have become increasingly popular as anti-obesity medications, but their long-term safety profile, particularly to cancer, has remained unclear. To address this, the investigators conducted a retrospective cohort study using electronic health record data from OneFlorida+, a large multicenter health research network, covering the period from 2014 to 2024. The analysis followed a target trial emulation approach to ensure robust comparisons between users and nonusers of GLP-1RAs.
The study population included 86,632 adults aged 18 years and older, all eligible for anti-obesity medications and free from prior cancer diagnoses. Participants were matched in a 1:1 ratio using propensity scores, resulting in two groups: 43,317 individuals who used GLP-1RAs and 43,315 who did not. The average age of participants was 52.4 years, and women constituted 68.2% of the sample.
Researchers evaluated the incidence of 14 cancers, including 13 obesity-related types—such as liver, pancreatic, colorectal, breast, and endometrial cancers—along with lung cancer.
The key findings of the study were as follows:
  • The overall cancer incidence rate was 13.6 per 1,000 person-years among GLP-1RA users compared to 16.4 per 1,000 person-years in nonusers.
  • This difference reflected a significantly lower overall cancer risk for GLP-1RA users, with a hazard ratio (HR) of 0.83.
  • GLP-1RA use was associated with a reduced risk of endometrial cancer, with an HR of 0.75.
  • The risk of ovarian cancer was also lower among GLP-1RA users, with an HR of 0.53.
  • Meningioma risk showed a decrease as well, with an HR of 0.69 in individuals taking GLP-1RAs.
  • A marginal, nonsignificant increase in kidney cancer risk was noted among GLP-1RA users, with an HR of 1.38.
The authors concluded that while GLP-1RA therapy appears to lower the overall risk of cancer in individuals with obesity, the possibly elevated risk for kidney cancer warrants attention. They emphasized the importance of long-term follow-up studies to better understand these associations and uncover the underlying biological mechanisms.
These findings add an important dimension to the discussion around GLP-1RA use, suggesting potential protective effects against several cancers while highlighting the need for ongoing safety evaluations as these drugs continue to be widely prescribed.
Reference:
Dai H, Li Y, Lee YA, et al. GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity. JAMA Oncol. Published online August 21, 2025. doi:10.1001/jamaoncol.2025.2681

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Stress Hyperglycemia Ratio and Hypertension Closely Associated with Stroke Risk: Study

A new study published in the BMC Cardiovascular Diabetology found the importance of a novel metabolic marker, the stress hyperglycemia ratio (SHR), in predicting stroke risk-especially when combined with hypertension.

The study used data from the China Health and Retirement Longitudinal Study (CHARLS), followed 9,682 stroke-free participants aged 45 years and older from 2011 through 2020. This research calculated SHR using 2 indicators, the fasting blood glucose and glycated hemoglobin (HbA1c), to integrate both short-term stress-induced changes and long-term glycemic levels.

The participants were divided into 4 groups based on whether they had high or low SHR and whether they had hypertension. Over a median follow-up of 8.43 years, covering more than 81,000 person-years, the study documented 764 new stroke cases. This translated to an incidence rate of 9.36 strokes per 1,000 person-years.

The individuals with both high SHR and hypertension faced the highest risk of stroke, with a hazard ratio of 2.94 when compared to the individuals with low SHR and no hypertension. Even when considered separately, both SHR and hypertension independently increased the risk of stroke.

The risk escalated progressively from having neither risk factor, to one of the two, and peaked in individuals with both. The subgroup analyses showed that this pattern held true across both men and women, as well as across different age categories.

To test the predictive strength of SHR, the team performed a receiver operating characteristic (ROC) curve analysis. While hypertension alone is a known predictor of stroke, adding SHR significantly improved the ability to discriminate who was at higher risk. The combined model achieved an area under the curve (AUC) of 0.653 which suggested better performance than traditional risk factors alone.

The findings suggest that SHR reflects both acute stress responses and chronic glucose imbalances, making it a more comprehensive indicator of metabolic stress than fasting glucose or HbA1c alone.

Overall, this research suggests that measuring SHR along with blood pressure screening could improve stroke risk assessment tools, particularly in populations already burdened by hypertension. This integrated approach may open the door to earlier interventions and more targeted prevention strategies, ultimately reducing the global stroke burden.

Reference:

He, Y., Cao, Y., Xiang, R., & Wang, F. (2025). Predictive value and robustness of the stress hyperglycemia ratio combined with hypertension for stroke risk: evidence from the CHARLS cohort. Cardiovascular Diabetology, 24(1), 336. https://doi.org/10.1186/s12933-025-02898-z

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Low-Dose Glucagon Reduces Exercise-Induced Hypoglycemia in Type 1 Diabetes, finds study

Exercise can dramatically lower blood glucose levels and trigger hypoglycemia in people with type 1 diabetes (T1D), even when insulin doses are adjusted. A new systematic review and meta-analysis, published in Diabetes Care, found that low-dose glucagon effectively reduces the risk of exercise-induced hypoglycemia and time spent below target glucose range (TBR) in this population.

The authors pooled data from 12 randomized and crossover trials involving 248 adolescents and adults with T1D. Low-dose glucagon reduced the risk of hypoglycemic events by about 46%, with a pooled risk ratio of 0.54 (95% CI 0.35–0.84). It also lowered TBR by an average of approximately 3.9 percentage points (95% CI –6.27 to –1.54), indicating a meaningful reduction in time spent with glucose below 3.9 mmol/L. Despite these promising effects, low-dose glucagon was associated with a higher rate of mild adverse events-a pooled risk ratio of 2.75 (95% CI 1.07–7.08)-though most were mild gastrointestinal symptoms or injection-site discomfort.

The authors emphasize that optimizing the dose and timing of glucagon relative to different exercise types and durations requires further investigation to ensure real-world effectiveness and safety.

They also note varying methodologies across included studies, suggesting cautious interpretation and the need for standardized protocols in future work. Clinically, this analysis supports using low-dose glucagon as an adjunctive strategy for preventing exercise-induced hypoglycemia in T1D, especially for active individuals facing daily glucose fluctuations. It can offer an alternative to carbohydrate loading-which may interrupt activity or risk hyperglycemia-while maintaining glycemic stability.

However, patients and clinicians should balance benefits against mild side effects and await more data on dosing strategies.

Reference:
Nørgaard, K., Laugesen, C., & Ranjan, A. G. (2025). Low-dose glucagon reduces exercise-induced hypoglycemia and time below range in type 1 diabetes: A systematic review and meta-analysis. Diabetes Care, 48(9), 1637–1645. https://doi.org/10.2337/dc25-0702

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Inhaled Insulin Shows Promise as Safe Option for diabetes management in Pregnancy: Study

A study published in Pregnancy suggests that inhaled technosphere insulin may be a safe alternative to rapid-acting insulin analogs for diabetes management during pregnancy. Cases demonstrated effective postprandial blood glucose control, and researchers recommend further studies comparing efficacy and safety with rapid-acting insulin analogs.

The case series, conducted by researchers from the University of Texas, reported outcomes in pregnant women with diabetes who used technosphere insulin during the gestational period. The investigators observed that inhaled insulin was effective at reducing post-meal glucose spikes, a key challenge in diabetes management during pregnancy. Importantly, no major maternal or neonatal safety concerns were identified.

Technosphere insulin, delivered via inhalation, has been previously studied as a non-invasive alternative to subcutaneous injections in patients with type 1 and type 2 diabetes. In pregnancy, where insulin requirements fluctuate due to hormonal changes, the ability to achieve tighter postprandial control without increasing hypoglycemia risk is particularly valuable.

The study highlights the potential benefits of inhaled insulin for pregnant patients who face challenges with multiple daily injections or who experience significant anxiety related to injectable therapy. Researchers also noted that patient adherence and satisfaction appeared higher with inhaled insulin, which could translate to improved long-term glycemic outcomes.

However, the authors caution that the current evidence is limited to small case series, and randomized controlled trials are needed to directly compare inhaled technosphere insulin with established rapid-acting analogs in pregnant populations. Until such data are available, the use of inhaled insulin in pregnancy should be considered experimental and reserved for carefully selected cases under close supervision.

The findings add to the growing discussion on expanding treatment options for diabetes management in pregnancy, where balancing maternal safety and fetal health remains critical.

Reference:
Parchem, J. G., Anderson, K. R., Alfaris, N., Sarma, V., Henry, R. R., & Demirci, C. (2025). Technosphere inhaled insulin use during pregnancy: Case series. Pregnancy. Advance online publication. https://doi.org/10.1097/PR9.0000000000000166

Keywords: inhaled insulin, technosphere insulin, pregnancy, diabetes management, gestational diabetes, type 1 diabetes, type 2 diabetes, maternal outcomes, neonatal safety, rapid-acting insulin analogs

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GLP-1 Agonists Tied to Slightly Increased Risk of New-Onset Diabetic Retinopathy: JAMA

USA: A large retrospective cohort study has revealed that the use of GLP-1 receptor agonists was associated with a 7% higher risk of developing new-onset diabetic retinopathy, although it did not increase the progression to proliferative retinopathy or diabetic macular edema. Regular eye screening is recommended for all patients taking these medications. 

The research, published in JAMA Network Open by David J. Ramsey, MD, PhD, MPH, from the Department of Ophthalmology, Tufts University School of Medicine, Boston, and colleagues, examined whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with sight-threatening eye complications in patients with type 2 diabetes (T2D). While GLP-1 RAs are increasingly used for glycemic control and weight loss, concerns remain regarding their ocular safety profile.

Using data from the TriNetX database, the investigators analysed records from 185,066 adults with T2D and a hemoglobin A1c of at least 6.5%. Participants were matched through propensity score methods based on whether they had received at least two GLP-1 RA prescriptions, spaced six months apart. The follow-up period spanned two years, with outcomes assessed using Cox proportional hazard models.

Key Findings

  • GLP-1 RA use was linked to a modest but statistically significant increase in the incidence of diabetic retinopathy (HR, 1.07).
  • There was no significant increase in cases of nonarteritic anterior ischemic optic neuropathy (HR, 1.26).
  • In patients with preexisting diabetic retinopathy, GLP-1 RAs did not associate with progression to proliferative diabetic retinopathy (HR, 1.06) or diabetic macular edema (HR, 0.98).
  • Treatment was associated with reduced rates of vitreous hemorrhage (HR, 0.74), neovascular glaucoma (HR, 0.78), and new-onset blindness (HR, 0.77).

The findings suggest that while GLP-1 RAs may slightly raise the risk of developing diabetic retinopathy, they do not accelerate its advancement to more severe stages and may even reduce the occurrence of serious vision-threatening complications.

The authors noted several limitations, including reliance on electronic health records, which may vary in coding practices and completeness, and the absence of consistent HbA1c measurements to assess the role of rapid glucose lowering. Additionally, the study could not account for all social determinants of health or differences in access to ophthalmic care, which might influence detection and treatment rates. The lack of eye examination data, reliance on administrative coding for blindness, and the inability to distinguish among specific GLP-1 agents also constrain the interpretation.

Despite these limitations, the researchers emphasize the importance of regular ophthalmologic monitoring for all T2D patients prescribed GLP-1 RAs, regardless of their baseline retinal status. Further studies are needed to clarify whether the protective association with certain complications translates into long-term reductions in vision loss.

Reference:

Ramsey DJ, Makwana B, Dani SS, et al. GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes. JAMA Netw Open. 2025;8(8):e2526321. doi:10.1001/jamanetworkopen.2025.26321

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Chitinase-3-like protein 1: a novel biomarker for liver disease diagnosis and management, finds study

The identification of Chitinase-3-like protein 1 (CHI3L1) as a crucial biomarker in liver disease is revolutionizing how clinicians approach the diagnosis, monitoring, and treatment of various liver conditions. As a member of the glycoside hydrolase family 18, CHI3L1 is recognized for its unique ability to bind to ligands and influence multiple pathophysiological processes, despite lacking enzymatic activity. This distinctive protein plays a key role in mediating cell proliferation, inflammation, fibrosis, and carcinogenesis.

Liver diseases, including hepatitis-related fibrosis, non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and hepatocellular carcinoma (HCC), represent significant global health challenges. Early and accurate diagnosis is critical to managing these conditions effectively, but traditional methods such as liver biopsy are invasive and not ideal for frequent monitoring. Serum biomarkers offer a non-invasive alternative, and CHI3L1 has emerged as a reliable marker, especially for diagnosing and staging hepatic fibrosis. Elevated levels of CHI3L1 correlate with fibrosis severity, particularly in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC), where it demonstrates superior diagnostic efficacy compared to conventional markers like hyaluronic acid (HA) and FIB-4.

In addition to its diagnostic capabilities, CHI3L1 plays a significant role in evaluating fibrosis progression and monitoring the efficacy of antiviral therapies. The protein’s levels increase proportionally with the advancement of liver fibrosis, making it a practical tool for assessing treatment response. Furthermore, CHI3L1 has shown promise in distinguishing between simple steatosis and non-alcoholic steatohepatitis (NASH), which is vital for identifying patients at higher risk of progressing to cirrhosis or HCC. Combining CHI3L1 with other markers, such as alpha-fetal protein (AFP) and platelet count, enhances diagnostic accuracy, particularly in detecting significant fibrosis and advanced stages of liver disease.

One of the most promising applications of CHI3L1 is its potential to predict the prognosis of HCC. Studies indicate that elevated CHI3L1 levels correlate with poor survival rates, especially after curative resection. When combined with AFP, CHI3L1 significantly improves the diagnostic accuracy for HCC, offering clinicians a more reliable method for early detection and risk assessment. The integration of CHI3L1 measurements with routine clinical practice could transform patient management by enabling more precise risk stratification and tailored therapies.

The growing body of evidence supports the use of CHI3L1 not only as a biomarker for liver fibrosis but also as a potential therapeutic target. As a key regulator of fibrosis and inflammation, targeting CHI3L1 could mitigate disease progression and improve outcomes for patients suffering from chronic liver diseases. Further research into the molecular mechanisms underlying CHI3L1’s actions will enhance our understanding of liver pathology and pave the way for novel therapeutic strategies.

Reference:

Chao Tian, Shizhou Deng, Ming Yang, Baochen Bai, Lai Wei, Role of chitinase-3-like protein 1 in liver diseases: A comprehensive review, Genes & Diseases,  https://doi.org/10.1016/j.gendis.2025.101653.

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UP DGME Releases NEET MDS Stray Vacancy Revised Schedule 2025

Lucknow: The Directorate General of Medical Education and Training (DGME), Uttar Pradesh, has released the revised time schedule for the Stray Vacancy Round of Online Counseling for UP NEET MDS-2025.

In continuation of the revised time-table issued by Medical Counselling Committee (MCC), New Delhi for counseling of NEET MDS course, the revised time-table of Stray Vacancy Round of online counseling for admission of state quota seats of MDS course in Government/Private Dental Colleges/Universities of the State is as follows:-

S.No. Description Dates Total Days
1 Date of online registration 26th
August 2025 (From 11:00 AM) to 29th August 2025 (Till 11:00 AM)		 03 days
2 Date of depositing registration fee and security Fee 26th
August 2025 (From 11:00 AM)
to 29th
August 2025 (Till 02:00 PM )		 04 days
3 Date of declaration of merit list 29th
August 2025		 01 days
4 Date of online choice filling 29th
August 2025 (From 05:00 PM) to 02nd September 2025 (Till 02:00 PM )		 04 days
5 Date of declaration of result of seat allotment 03rd September 2025 01 days
6 Date for downloading allotment letters and admission process 04th
September 2025 to 06th September 2025 & 08th September 2025		 04 days

To participate in the stray vacancy round, it is mandatory for all eligible candidates to get fresh registration done by paying Rs. 3000/- (Rs. Three Thousand only) as online registration fee separately.

To view the official notice click here: https://medicaldialogues.in/pdf_upload/1919-and-1921-298454.pdf

The Medical Counselling Committee (MCC) has extended the National Eligibility and Entrance Test-Master of Dental Surgery (NEET-MDS) Stray vacancy Round Counselling schedule for the academic year 2025 for the All India Quota and State Quota seats.

As per the new schedule, the NEET-MDS Stray vacancy Round counselling for the students who qualified the UG medical entrance test will now commence on 26th July for the All India Quota/Deemed/Central Universities seats. Whereas, the academic session for the UG courses shall commence from 8th September 2025.

Also Read:MCC Extends NEET MDS 2025 Stray Vacancy Round Counselling, Registration Begins August 26

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MBBS, BDS 2025: Adhere to Court orders, NMC guidelines- TN private medical colleges warned

Tamil Nadu- The Tamil Nadu private medical colleges have been warned to adhere to Supreme Court, High Court orders and the National Medical Commission guidelines with respect to the MBBS and BDS admissions 2025.

The Tamil Nadu (TN Health) has issued a notification for all the Deans and Principals of Self-Financing Medical Institutions regarding the admission into the MBBS & BDS counselling for the academic year 2025-2026.

Through the notification, all the Deans and Principals of Self-Financing Medical Institutions are advised to strictly adhere to the Directions of the Hon’ble Supreme Court of India and High Court orders and National Medical Commission (NMC) guidelines without fail.

Also Read: TN NEET Round 1 Counselling Seat Allotment Result OUT, Candidates Must Report by August 24

However, if any Self Financing Institutions refuse to admit the candidate in any round of MBBS & BDS counselling for the academic year 2025-2026 and demand a Higher fee other than the fee prescribed by the Fee Fixation Committee, strict action will be initiated against the institutions by the Government.

On receipt of any specific complaints from the candidates, action will be taken against the respective institution, including the withdrawal of approval or cancellation of affiliation of the college through the appropriate authorities.

The Tamil Nadu National Eligibility and Entrance Test-Undergraduate (NEET UG) Counselling 2025 Round 1 Seat Allotment Result on August 18, 2025. 

On this, Medical Dialogues has reported that candidates who have secured their seats in MBBS and BDS courses must download their allotment letter and report to their allotted colleges/institutions with their official personal and academic documents to proceed with the admission procedures to confirm their seats by August 24, 2025. Failure to comply will result in the cancellation of the seat.

However, those who are not allotted any seat in Round 1 will get a second chance in Round 2 counselling, for which the schedule is likely to be released soon. Those who want to upgrade the seat can also apply for the second round.

To view the notification, click the link below

https://medicaldialogues.in/pdf_upload/tn-health-warns-self-financing-medical-colleges-for-mbbs-bds-admission-2025-26-298491.pdf

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