This living systematic review and network meta-analysis (NMA) compiles up-to-date evidence on benefits, harms, and uncertainties for medications used in adults with type 2 diabetes. Using Medline and Embase searches through July 31, 2024, the authors included randomized controlled trials of at least 24 weeks comparing diabetes drugs with placebo, standard care, or each other, and they plan to update the analysis at least twice yearly. The current iteration includes 869 trials with 493,168 participants, covering 13 drug classes (63 drugs) and 26 outcomes, with an interactive tool provided to show risk-stratified absolute effects because benefits vary substantially depending on baseline cardiovascular and kidney risk.

Overall, moderate-to-high certainty evidence supports the well-established cardiovascular and kidney benefits of SGLT-2 inhibitors, GLP-1 receptor agonists (GLP-1RAs), and finerenone. For weight loss, tirzepatide showed the largest reductions (about −8.6 kg; moderate certainty) and orforglipron also showed substantial loss (about −7.9 kg; low certainty), followed by several other GLP-1RAs. Authors also detail important medication-specific harms. Evidence for effects on other complications (eg, neuropathy, visual impairment) is low/very low, and there remains uncertainty about potential dementia risk reduction with GLP-1RAs.

Reference: Nong K, Jeppesen BT, Shi Q, et al. Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis. BMJ. 2025;390:e083039. doi: 10.1136/bmj-2024-083039.

In the pediatric INHALE-1 trial (n=230; ages 4–17, ~98% with type 1 diabetes), technosphere inhaled insulin delivered HbA1c outcomes at 26 weeks that were comparable to injected rapid-acting analogs while all participants continued basal insulin and used continuous glucose monitor. Mean HbA1c was essentially similar between groups; a sensitivity analysis (excluding one nonadherent outlier) met noninferiority (Δ≈0.14%, P=.026). Time-in-range was not different (39% vs 41%; P=.38). Because technosphere insulin acts faster and clears sooner, effective use often required multiple inhalations per meal and dose “tune-ups.” Dosing units are not 1:1 with injections; participants ultimately averaged approximately 3 times the analog unit count by week 26.

Secondary outcomes favored inhaled insulin on patient-centered measures: adolescents and parents reported higher treatment satisfaction, and body mass index percentile was lower (Δ −4.2; P=.009), consistent with less weight gain. Safety signals were acceptable and broadly similar: severe hypoglycemia was rare (2 vs 1), no pulmonary function decline was detected, and cough during inhalation (typically mild) occurred in 17%. No diabetic ketoacidosis occurred with technosphere insulin (one event with analogs). While technosphere insulin is not yet FDA-approved for pediatric patients, investigators argued the data support considering an expanded indication and highlight use cases such as basal-plus-inhaled regimens and potential future integration with automated insulin delivery.

Reference: Monostra M. Inhaled insulin safe, effective for children with diabetes. Healio. Published June 22, 2025. Accessed December 16, 2025. https://www.healio.com/news/endocrinology/20250622/inhaled-insulin-safe-effective-for-children-with-diabetes

The FDA has updated the criteria for the “healthy” nutrient content claim to help consumers identify foods that align with dietary recommendations. This claim, which manufacturers can voluntarily use, provides a quick signal on food labels to help consumers choose foundational foods for healthy eating patterns. The initiative is part of the FDA’s broader effort to reduce diet-related chronic diseases and promote health equity, particularly among racial and ethnic minority groups and individuals with lower socioeconomic status.

To use the “healthy” claim, food products must meet specific criteria, including containing a certain amount of food from recommended food groups like fruits, vegetables, and whole grains, and adhering to limits for saturated fat, sodium, and added sugars. The update expands the range of foods eligible for the claim, including nuts, seeds, and certain oils, which were previously excluded. Manufacturers have three years to comply with the new criteria, though they can adopt them sooner. The FDA is also exploring the development of a standardized symbol to make it easier for consumers to identify products that meet the “healthy” criteria.

Reference: U.S. Food and Drug Administration. FDA Finalizes Updated “Healthy” Nutrient Content Claim. FDA. Published December 19, 2024. Accessed January 20, 2025. https://www.fda.gov/food/hfp-constituent-updates/fda-finalizes-updated-healthy-nutrient-content-claim

In a study, researchers aimed to evaluate how age and sex influence the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors in managing hyperglycemia and reducing major adverse cardiovascular events (MACEs) in individuals with type 2 diabetes. The analysis included 601 trials with over 309,000 participants, assessing both HbA1c reduction and MACEs. Results showed that SGLT2 inhibitors provided less HbA1c reduction with increasing age across all therapy regimens, whereas GLP-1 receptor agonists resulted in greater HbA1c lowering with age for monotherapy and dual therapy, but not for triple therapy. DPP4 inhibitors showed slightly better HbA1c lowering in older individuals, especially for dual therapy. Additionally, SGLT2 inhibitors were more effective in reducing the risk of MACEs in older participants, while GLP-1 receptor agonists had a stronger effect in younger participants.

The findings suggest that SGLT2 inhibitors and GLP-1 receptor agonists are both effective in reducing the risk of MACEs, but their efficacy may differ based on age. SGLT2 inhibitors are more cardioprotective in older patients despite a smaller reduction in HbA1c, whereas GLP-1 receptor agonists offer more cardioprotection in younger individuals. The authors did not find consistent evidence of sex-related differences in treatment efficacy, providing reassurance that the observed effects were not significantly influenced by gender. These results underscore the importance of considering age when selecting diabetes treatments that also reduce cardiovascular risk.

Reference: Hanlon P, Butterly E, Wei L, et al. Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis. JAMA. 2025;333(12):1062-1073. doi: 10.1001/jama.2024.27402.

A double-blind trial was conducted to assess the effects of empagliflozin in patients with heart failure and preserved ejection fraction. A total of 5,988 patients with class II–IV heart failure and an ejection fraction greater than 40% were randomly assigned to receive either empagliflozin (10 mg daily) or a placebo, in addition to their usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.

Over a median follow-up of 26.2 months, empagliflozin significantly reduced the risk of the primary outcome compared to placebo, with 13.8% of patients in the empagliflozin group experiencing a primary outcome event, vs 17.1% in the placebo group (hazard ratio, 0.79; P<0.001). The reduction was primarily driven by fewer hospitalizations for heart failure in the empagliflozin group. The benefit of empagliflozin was consistent in patients with or without diabetes. However, there was a higher incidence of uncomplicated genital and urinary tract infections and hypotension in the empagliflozin group. In conclusion, empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and preserved ejection fraction, irrespective of diabetes status.

Reference: Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461. doi: 10.1056/NEJMoa2107038.

Recent clinical guidelines recommend avoiding "diabetes overtreatment" in older individuals with type 2 diabetes (T2D), which refers to excessively low glycemia that increases the risk of side effects like hypoglycemia. This study, part of the HYPOAGE cohort, used continuous glucose monitoring (CGM) data to assess the incidence and predictive value of hypoglycemia associated with these proxy definitions in older insulin-treated patients with T2D. The researchers found no significant association between HbA1c-based proxy definitions of overtreatment and the occurrence of hypoglycemia.

The study highlighted the high prevalence of hypoglycemia, particularly in overtreated patients, but found that both fixed and individualized HbA1c thresholds had low predictive value for hypoglycemia. These findings challenge the reliance on HbA1c alone as a marker for overtreatment, suggesting that CGM-based definitions may be more effective. However, further research is needed to validate these findings and explore alternative methods for identifying older patients at risk for hypoglycemia due to intensive glucose-lowering therapies. This study emphasizes the need for revised approaches to managing diabetes in older patients to reduce the risks associated with overtreatment.

Reference: Christiaens A, Boureau AS, Guyomarch B, et al. Diabetes Overtreatment and Hypoglycemia in Older Patients With Type 2 Diabetes on Insulin Therapy: Insights From the HYPOAGE Cohort Study. Diabetes Care. 2025;48(1):61-66. doi: 10.2337/dc24-1058. 

A recent study published in Diabetes, Obesity and Metabolism shows that initiating an automated insulin delivery (AID) system improves glycemic control in children and adolescents with type 1 diabetes (T1D) who struggle to achieve optimal control with traditional methods. The study, led by Maaria Kiilavuori, MD, from the University of Helsinki, included 79 patients aged 7 to 16 years, all of whom had hemoglobin A1C levels greater than 53 mmol/mol (7%).

The findings revealed that after starting the AID system, participants experienced significant improvements in glycemic control. Between 0 to 3 months, time in tight range and time in range increased by an average of 11.7% and 18.1%, respectively. Hemoglobin A1c and mean sensor glucose levels also decreased significantly, and these positive effects were maintained over the 12- and 24-month follow-up periods. The researchers concluded that AID could be a viable treatment option for pediatric patients with T1D, particularly in those with difficulties in managing their diabetes effectively.

Reference: Solomon L. Automated Insulin Delivery System Improves Glycemic Control in Youth. HealthDay. Published December 12, 2024. Accessed January 20, 2025. https://www.healthday.com/healthpro-news/diabetes/automated-insulin-delivery-system-improves-glycemic-control-in-youth

Spinal cord stimulation (SCS) has emerged as an effective treatment for managing pain from diabetic peripheral neuropathy (DPN), especially when other therapies are ineffective. This FDA-approved therapy works by delivering electrical impulses to the spinal cord, blocking pain signals before they reach the brain. Following a trial period, patients undergo a full implant procedure, which can significantly reduce pain and improve overall well-being. Studies have shown that SCS devices are highly effective in managing chronic pain, offering long-term relief and even improvements in sleep and quality of life.

DPN is a common complication of diabetes, causing symptoms like pain, numbness, and tingling in the extremities. Managing DPN typically involves blood sugar control and medications, but for many, these treatments are insufficient. SCS offers an alternative, especially for patients with persistent nerve pain. The benefits in terms of pain relief and quality of life make it a promising option for many people with DPN. With ongoing research into different SCS systems and their effectiveness, spinal cord stimulation provides hope for long-term pain management for those suffering from painful diabetic neuropathy.

Reference: Vidovszky A. Spinal Cord Stimulation: Overview, How It’s Done, Benefits. The diaTribe Foundation. Published January 13, 2025. Accessed March 4, 2025. https://diatribe.org/diabetes-complications/spinal-cord-stimulation-overview-how-its-done-benefits?omhide=true&utm_source=diaTribe&utm_campaign=fd6a183503-learn_2025-01-14&utm_medium=email&utm_term=0_22467a8528-fd6a183503-468520015

This guideline provides clinical practice guidance for treating diabetes in older adults, particularly those over the age of 65, as type 2 diabetes is becoming more prevalent in this age group. Aging exacerbates the metabolic effects of diabetes, accelerating the progression of complications. The guidelines aim to present evidence, primarily from controlled trials, on therapeutic options and their outcomes for this population, with a focus on avoiding unnecessary or harmful side effects. The goal is to offer healthcare providers strategies that will benefit older adults with diabetes, addressing both type 1 and type 2, while considering the impact of aging on their overall health.

A survey of older adults with diabetes revealed a wide variety of health conditions that affect their quality of life, with many participants reporting multiple comorbidities. About 40% of respondents ranked diabetes as their most important health concern, but other conditions like hypertension, heart disease, and depression were also significant. The survey results highlight the importance of tailoring treatment based on an individual’s health status and cognitive function, with some participants indicating that diabetes did not dominate their health concerns. The findings emphasize the need for clear communication between clinicians and patients regarding the risks and benefits of different therapeutic strategies.

Reference: LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi: 10.1210/jc.2019-00198. 

Researchers of a large, randomized trial evaluated the cardiovascular effects of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes at high cardiovascular risk. Over a median of 3.1 years, patients received either empagliflozin (10 mg or 25 mg daily) or placebo, in addition to standard care. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Among over 7,000 patients, the empagliflozin group showed a modest but statistically significant reduction in the primary composite outcome compared to placebo (hazard ratio, 0.86; P=0.04).

While rates of myocardial infarction and stroke were similar between groups, empagliflozin was associated with substantial reductions in death from cardiovascular causes (38% relative risk reduction), hospitalization for heart failure (35% reduction), and death from any cause (32% reduction). The key secondary outcome, which added unstable angina to the primary composite, did not show a statistically significant difference. Although genital infections were more frequent in the empagliflozin group, there was no increase in serious adverse events. Overall, empagliflozin significantly reduced mortality and heart failure hospitalizations in high-risk patients with type 2 diabetes.

Reference: Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. doi: 10.1056/NEJMoa1504720

A new study has found that people taking semaglutide may face a slightly increased risk of developing nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition that causes sudden vision loss in one eye due to reduced blood flow to the optic nerve. The research showed a 32% increased relative risk of NAION among semaglutide users, although the absolute risk remains low—about 14 cases per 100,000 person-years. These findings align with a prior 2024 study from Mass Eye and Ear that reported a stronger link, suggesting a fourfold increased risk.

Despite this association, experts urge caution rather than alarm. The new study found no significantly increased risk of NAION when comparing semaglutide to other GLP-1 receptor agonists. In an accompanying editorial, researchers emphasized the broad systemic benefits of semaglutide—such as improved diabetes control, weight loss, and reduced cardiovascular risks—and advised against discontinuing the medication solely based on this potential eye risk. However, added caution may be warranted for patients with a history of vision loss or other optic nerve conditions. Further research is needed to better understand the underlying mechanisms and confirm the link.

Reference: Thompson D. Ozempic, Wegovy Linked To Potential Vision Loss. HealthDay. Published February 24, 2025. Accessed April 22, 2025. https://www.healthday.com/health-news/drug-center/ozempic-wegovy-linked-to-potential-vision-loss

Researchers of a recent single-arm prospective trial evaluated the safety and efficacy of the Omnipod 5 automated insulin delivery (AID) system in adults with type 2 diabetes using insulin. Conducted across 21 US clinical centers, the study included 305 participants aged 18 to 75, most of whom were using multiple daily injections or basal insulin. After 13 weeks of AID use, participants experienced a significant reduction in hemoglobin A1c levels—from an average of 8.2% to 7.4%—as well as a 20 percentage point increase in time spent within the target glucose range (70–180 mg/dL). These results were consistent across various demographics and medication backgrounds, including those not taking GLP-1 receptor agonists or SGLT-2 inhibitors.

The trial also demonstrated that AID use did not increase hypoglycemia risk, with time spent in low glucose ranges remaining noninferior to standard therapy. Only one case of severe hypoglycemia occurred, and no instances of diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome were reported. These findings suggest that AID systems, like Omnipod 5, could offer a safe and effective insulin management option for adults with type 2 diabetes, even in a diverse and medically complex patient population.

Reference: Pasquel FJ, Davis GM, Huffman DM, et al. Automated Insulin Delivery in Adults With Type 2 Diabetes: A Nonrandomized Clinical Trial. JAMA Netw Open. 2025;8(2):e2459348. doi: 10.1001/jamanetworkopen.2024.59348. 

Efforts to reduce delays in diagnosis and treatment of cardiorenal and metabolic diseases—such as obesity, metabolic syndrome, prediabetes, diabetes, and heart failure—require a shift toward earlier, more intensive intervention. Despite the availability of effective therapies, only a small percentage of Americans meet clinical targets for risk management, and cardiometabolic health has worsened overall. A volunteer task force of experts has created recommendations that address this gap, emphasizing primary and secondary prevention through early screening, timely diagnosis, and combination treatment.

The guidelines promote a proactive approach, urging clinicians to initiate treatment promptly and avoid sequential, low-dose regimens that delay goal attainment and worsen outcomes. Weight loss, physical activity, dietary modifications, and modern pharmacologic strategies—including GLP-1 receptor agonists, SGLT2 inhibitors, and statins—are central to this strategy. This early, intensive approach targets the entire continuum from obesity to type 2 diabetes, atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure, aiming to reduce complications, improve quality of life, and extend lifespan. Furthermore, the use of advanced diagnostics and patient-monitoring technologies can improve adherence and outcomes. The recommendations underscore the urgent need for coordinated, guideline-driven action to reverse the rising burden of cardiometabolic disease.

Reference: Handelsman Y, Butler J, Bakris GL, et al. Early intervention and intensive management of patients with diabetes, cardiorenal, and metabolic diseases. J Diabetes Complications. 2023;37(2):108389. doi: 10.1016/j.jdiacomp.2022.108389.

This Mendelian randomization (MR) study investigated whether three classes of cholesterol-lowering drugs—HMGCR inhibitors (eg, statins), PCSK9 inhibitors, and NPC1L1 inhibitors—causally affect the risk of diabetic microvascular complications. Using genetic data from genome-wide association studies, researchers examined the relationship between these drug targets and key complications including diabetic nephropathy, retinopathy, and neuropathy. Genetic proxies for drug exposure were analyzed for their impact on LDL-C levels and downstream microvascular disease in patients with diabetes, with coronary artery disease used as a positive control.

Results revealed that HMGCR inhibition was strongly associated with increased risks of diabetic nephropathy, retinopathy, and neuropathy. Similarly, PCSK9 inhibition was linked to elevated risks of nephropathy and neuropathy. In contrast, inhibition of NPC1L1 appeared protective against diabetic retinopathy. These findings suggest that while certain cholesterol-lowering therapies may increase microvascular risk in diabetes, NPC1L1 inhibitors could hold potential for targeted protection—highlighting the need for personalized lipid management in diabetic populations.

Reference: Yang B, Yao B, Zou Q, Li S, Yang S, Yang M. Causal Association Between Cholesterol-Lowering Drugs and Diabetic Microvascular Complications: A Drug-Target Mendelian Randomization Study. J Diabetes Res. 2025;2025:3661739. doi: 10.1155/jdr/3661739.