Patients with type 1 diabetes (T1D) who have risk factors such as obesity and hypertension can develop insulin resistance over time, a characteristic typically associated with type 2 diabetes (T2D). This condition, known as double diabetes, combines the characteristics of T1D and T2D.
“About a quarter of patients with T1D develop metabolic syndrome,” said Thomas Haak, MD, chief physician at the Diabetes Center Bad Mergentheim, Bad Mergentheim, Germany, and former president of the German Diabetes Society (DDG), speaking at the “Innere Medizin fachübergreifend — Diabetologie grenzenlos” congress held on February 7 and 8 in Munich, Germany.
“Double diabetes exists and requires appropriate treatment,” said Haak.
Patients with T1D often have elevated triglyceride levels and high blood pressure, with women affected more often than men. This combination doubles the risk for coronary heart disease and increases the risk for stroke, diabetic foot, and nephropathy.
Patients with T1D must take insulin throughout their lives to manage their blood glucose levels. Haak explained that the first sign of insulin resistance in T1D is an increased insulin requirement exceeding 100 units/d.
Diagnosis involves assessing the clinical presentation of T1D, measuring C-peptide levels in the blood, and considering family history. Relevant clinical parameters include obesity, body mass index (BMI), waist circumference, and metabolic syndrome, particularly triglyceride levels and hypertension.
According to the 2023 S3 guideline of the DDG on T1D management, more than half of patients with T1D have a BMI > 25. The prevalence of metabolic syndrome in this population is increasing, mirroring trends observed in the general population.
Complications and Risks
A 2016 German study examined more than 30,000 individuals with T1D for signs of metabolic syndrome and its complications. The findings revealed that 1 in 4 patients met the criteria for metabolic syndrome, defined by obesity, high blood pressure, and dyslipidemia, and could be classified as having double diabetes.
These patients had higher rates of micro- and macrovascular comorbidities, regardless of the glycemic control. The DDG guidelines recommend addressing each component of metabolic syndrome in patients with T1D.
Treatment: What Works, What Does Not?
“So how do we best manage this condition?” asked Haak. A 2024 consensus report from the American Diabetes Association identified three key strategies:
- Lifestyle changes, such as high-fiber diets
- Bariatric surgery
- Medication
Haak emphasized that dietary adjustments are an effective method, focusing on reducing fat and carbohydrate intake. He highlighted the effectiveness of an initial 12-day “liver fast,” a protein-restricted diet that helps improve metabolic parameters.
Short-term dietary interventions, such as two consecutive “oat days” during which only oats are consumed, are beneficial for insulin resistance.
In clinical practice, combining dietary interventions with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has yielded promising results. However, Haak noted that timing is critical due to the potential for gastrointestinal side effects associated with GLP-1 RAs.
While bariatric surgery can be effective for obesity in T1D, it carries a risk for complications and requires careful patient selection as well as psychological and medical follow-up.
Metformin is effective for glycemic control but is not indicated for T1D alone, Haak continued. However, metformin can be used in patients with T1D and T2D. “Metformin should definitely be included in the concept,” he said, though it is not suitable for long-term use due to the risk for hypoglycemia.
The DDG guidelines highlight the role of metformin in managing insulin resistance in patients with T1D.
SGLT2 Inhibitors: A No-Go
For patients with well-controlled T1D, GLP-1 RAs can be used to manage obesity and insulin resistance, Haak explained. However, caution is required due to the increased risk for diabetic ketoacidosis. While these medications are not contraindicated, their costs are not reimbursed in many healthcare systems.
Haak referenced findings from the DEPICT-1 study, which showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors in T1D can lower insulin requirements and reduce hypoglycemia risk but are also linked to ketoacidosis and other adverse events.
”SLGT2 inhibitors are contraindicated in T1D; the risk is too high,” Haak said, noting the available alternative treatments.
The guidelines do not confirm the safety and efficacy of SGLT2 inhibitors as an add-on treatment for T1D due to inconsistent results. Further studies are required to evaluate their safety.
From www.medscape.com
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Semaglutide and tirzepatide hold potential to transform type 1 diabetes treatment, says GlobalData
A recent study published in Diabetes Technology & Therapeutics has demonstrated that the off-label use of semaglutide and tirzepatide leads to significant reductions in HbA1c levels and body weight among adults with type 1 diabetes (T1D). These findings suggest a potential new therapeutic approach for improving glycemic control and addressing obesity in T1D, an area with few pharmacologic advancements beyond insulin therapy, according to GlobalData, a leading data and analytics company.
GlobalData’s latest report, “Type 1 Diabetes: Seven-Market Drug Forecast and Market Analysis”, forecasts substantial growth in the T1D market across the seven major markets (7MM). With the potential introduction of non-insulin pharmacologic therapies, the market is expected to expand at a compound annual growth rate (CAGR) of 13.3%, increasing from $2.2 billion in 2023 to $9.9 billion in 2033.
Sulayman Patel, Pharma Analyst at GlobalData, comments: “The findings are particularly relevant as the T1D market continues to evolve, with a growing emphasis on adjunctive therapies to complement insulin regimens. The promising data on semaglutide and tirzepatide in T1D highlights the potential for GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists to reshape diabetes management beyond type 2 diabetes. These findings suggest that targeted therapies could complement insulin treatment, providing additional benefits in glycemic control and weight management.”
The study analyzed data from 150 adults with T1D, divided into semaglutide, tirzepatide, and control groups. After one year, the tirzepatide group experienced an average weight loss of 21.4% and a 0.67 percentage point reduction in HbA1c, while the semaglutide group saw a 9.1% weight loss and similar HbA1c improvements. In contrast, the control group showed no significant changes in weight or glycemic control. These results highlight the potential for these therapies to address critical unmet needs in T1D management.
Key opinion leaders (KOLs) interviewed by GlobalData emphasize the need for additional pharmacologic options beyond insulin to improve glycemic outcomes in T1D. One US-based KOL noted: “Only 20% to 30% of patients achieve their glycemic targets, underscoring the urgent need for effective adjunctive therapies.”
Meanwhile, a Japanese KOL added: “In cases where endogenous insulin secretion is completely depleted, glucose fluctuations remain a significant challenge, highlighting the necessity for alternative therapeutic approaches.” These insights reinforce the importance of expanding treatment options for individuals with T1D.
Patel adds: “From a pharmaceutical market perspective, the off-label success of semaglutide and tirzepatide in T1D carries significant implications for drug development and commercialization. With growing interest in adjunctive therapies, pharmaceutical companies may pursue formal clinical trials to secure regulatory approval for these agents in T1D. However, challenges remain, including safety considerations, regulatory hurdles, and the need for reimbursement models that support expanded indications. The adoption of these therapies could also impact insulin utilization patterns, leading to shifts in market dynamics.”
Despite the promising results, further research is needed before GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists can be integrated into standard T1D treatment. The potential risk of hypoglycemia, insulin dose adjustments, and patient variability in response requires further evaluation through large-scale, randomized controlled trials. Regulatory agencies will demand comprehensive efficacy and safety data before considering label expansions for these agents in T1D.
Patel concludes: “These findings reveal that semaglutide and tirzepatide may not only support glycemic control and weight loss, but also offer a new avenue for mitigating insulin resistance in T1D which is a factor increasingly recognized a s barrier to optimising diabetes management. As research continues to explore their long-term safety and efficacy, semaglutide and tirzepatide could offer a meaningful shift in how T1D is managed—potentially bridging the gap between insulin dependency and broader metabolic control.”
*7MM = US, France, Germany, Italy, Spain, the UK, and Japan
- This press release was written using data and information sourced from proprietary databases, primary and secondary research, and in-house analysis conducted by GlobalData’s team of industry experts
Press release GlobalDataMediaCentre.com
