Glargulis provides a new strategy for the initial injection treatment of Chinese diabetic patients with poorly controlled OAD

Editor's note

During the 84th Annual Meeting of the United States Diabetes Association (ADA 2024), the first head-to-head trial of glargollix plus bidecoglutamon for poorly controlled oral hypoglycemic drugs (OAD) led by Professor Mu Yiming of the PLA General Hospital - China Rock Study SoliD[1] data was officially released, bringing a new treatment strategy for patients with type 2 diabetes mellitus (T2DM) with poorly controlled OAD. Professor Yiming Mu was invited to introduce the background and highlights of SoliD research, the enlightenment and significance of the study for clinical practice, and the prospect of the application of fixed-ratio compound preparation (FRC) in the management of T2DM in the future.

Background and highlights of SoliD's research

Prof. Mu Yiming: In the field of diabetes treatment, insulin injection is undoubtedly a crucial part. At present, the traditional treatment model for T2DM is "sequential" therapy, that is, monotherapy to monotherapy and then to combination therapy. The introduction of insulin or glucagon-like peptide-1 receptor agonists (GLP-1RAs) is considered as treatment when OAD monotherapy or dual agents have failed.

However, although initiation of insulin therapy is effective for glycemic control, it may also be associated with a risk of hypoglycemia and weight gain. In China, in particular, there is a high rate of overweight and obesity among diabetic patients [2], so these side effects may adversely affect the overall health of patients, such as hypertension, dyslipidemia, and difficulty in glycemic control.

To address this challenge, many guidelines recommend the preferential use of GLP-1RA in the event of OAD failure due to its cardiovascular, blood pressure, lipid, and weight improvement [3-4]. However, for patients with weak islet function, insulin therapy is necessary. In this context, the fixed-ratio combination of GLP-1RA and basal insulin has gradually attracted much attention. On the one hand, insulin glargine (basal insulin analogue) can mimic the body's physiological insulin secretion and smoothly control 24-hour basal blood glucose. On the other hand, lisinatide (GLP-1RA) promotes insulin secretion and lowers blood glucose peaks according to the degree of blood sugar increase during meals, while delaying gastric emptying, controlling appetite, and strengthening blood glucose control after meals. Synergistically improve insulin resistance and β cell dysfunction, leading to islet benefits, leading to better blood sugar control, reduced weight gain, and reduced risk of hypoglycemia.

Based on this concept, the China Panshi SoliD study was developed to evaluate the efficacy of adding a fixed-ratio combination of insulin glargine and risinatide (referred to as glargine) in T2DM patients with one or both OADs. The SoliD study was conducted in a randomized, open-label, active-controlled, multicenter design with a 24-week head-to-head comparison with Deglu aspart. The results showed that the change of glycosylated hemoglobin (HbA1c) from baseline to 24 weeks from baseline to 24 weeks reached the non-inferiority (P<0.001) and superiority (P=0.003) criteria, with a statistically significant difference of -0.20% between the two groups. In addition, 24 weeks of glargin treatment resulted in a weight loss of 1.49 kg, which also met the statistically superior criteria.

This study provides a new treatment option for patients with T2DM after OAD failure, especially for those concerned about the risk of hypoglycemia and weight gain. Glargulox is generally safe and well tolerated, and has shown benefits such as lower risk of hypoglycemia and weight loss while lowering blood glucose, reflecting its unique advantages in the treatment of diabetes mellitus and providing strong support for clinical application.

Clinical implications for the results of the SoliD study

Prof. Yiming Mu: At present, patients with T2DM who are poorly controlled by OAD in mainland China still face large unmet needs, such as patients treated with premixed insulin, who still have unsatisfactory HbA1c control, and have problems such as hypoglycemia, risk of weight gain, and difficulty in following multiple injections [5]. The results of the SoliD study suggest that the basal insulin/GLP-1RA combination of glargin provides a better initial injection option for patients with T2DM who are poorly controlled by OAD therapy than Degludec aspart. It should be emphasized that the SoliD study was conducted in Chinese patients, and based on the data and evidence of the Chinese population, glargon is undoubtedly an option worth considering for Chinese diabetic patients.

Treatments for diabetes are varied, but the pathophysiology is extremely complex and may vary from patient to patient. Therefore, there is a clinical expectation that there will be more diversified treatment methods to meet the needs of different patients. At present, hypoglycemia is undoubtedly the main goal of treatment, but we also want to avoid significant side effects during treatment, especially hypoglycemia, which is often associated with insulin therapy. For some patients with poor glycemic control, relatively weak islet function, and who require insulin therapy but want to avoid the risk of weight gain and hypoglycemia, glargolis may be a more appropriate option.

Diabetes treatment is a long-term process, and in addition to adhering to treatment, clinicians also hope that they can avoid unnecessary side effects as much as possible in addition to the benefits of lowering blood sugar in the long term. From this point of view, SoliD research reflects its important value and provides a new treatment model for the majority of diabetic patients, which undoubtedly brings new hope and possibilities to the field of diabetes treatment.

Future prospects for FRC in T2DM management and research

Prof. Mu Yiming: In the process of diabetes treatment, we should not only pay attention to weight management and blood sugar control, but also provide reasonable treatment options for patients with relatively insufficient pancreatic islet function. Traditional insulin therapy may require multiple injections, which not only increases the burden of treatment for patients, but also increases the risk of hypoglycemia and the likelihood of weight gain, which we strongly want to avoid.

In recent years, the combination of basal insulin and GLP-1RA has been especially suitable for patients who not only face difficulties in weight management or OAD failure, but also have insufficient islet function due to its strong hypoglycemic effect, low risk of hypoglycemia, small impact on body weight, fewer injections, and good patient compliance. Therefore, it has been highly recommended in major diabetes treatment guidelines and consensus at home and abroad, and has been more and more highly recognized, including the 2023 edition of the United States Clinical Endocrine Society (AACE) Consensus Statement: Comprehensive Management Process for Type 2 Diabetes, 2024 ADA "Diabetes Diagnosis and Treatment Standards", "China Type 2 Diabetes Prevention and Treatment Guidelines (2020 Edition)", 2023 China "Clinical Expert Recommendations for the Treatment of Type 2 Diabetes Mellitus/Glucagon-like Peptide-1 Receptor Agonist Combination Preparations", " Guidelines for the diagnosis and treatment of diabetes mellitus in the elderly in China (2024 edition) [6-10] and others. It is foreseeable that more of these combination treatment options will be available in the future, helping to improve weight and blood sugar control with fewer side effects.

As mentioned earlier, the SoliD study demonstrated in the Chinese population that glarizol can help more diabetic patients with poorly controlled OAD achieve early quality goals, thereby improving clinical outcomes, and therefore, it can be used as the preferred treatment for the initial injection therapy of poor OAD treatment in Chinese T2DM patients.

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