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Introduction The progressive nature of type 2 diabetes necessitates treatment intensification. This often involves intensification with oral antidiabetic drugs (OADs) initially, followed by other agents, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), with the majority of patients eventually requiring insulin therapy. Therefore, this trial aimed to investigate the efficacy of IDegLira (combination of insulin degludec and liraglutide) in controlling glycemia in adults with type 2 diabetes who were inadequately controlled on a GLP-1RA and OADs. Methods In this 26-week open-label phase 3b trial, patients on maximum-dose GLP-1RA therapy (liraglutide once daily or exenatide twice daily) with metformin alone or with pioglitazone and/or sulfonylurea were randomized 2:1 to IDegLira once daily ( n  = 292) or to unchanged GLP-1RA therapy ( n  = 146), continuing OADs at the pre-trial dose. Results After 26 weeks, HbA 1c reductions were superior with IDegLira versus unchanged GLP-1RA; estimated treatment difference −0.94% (−10.3 mmol/mol), p  < 0.001. Mean HbA 1c reduced from 7.8% to 6.4% (61.5 to 46.9 mmol/mol) with IDegLira and from 7.7 to 7.4% (60.8 to 57.1 mmol/mol) with unchanged GLP-1RA. With IDegLira, 75% and 63% of patients achieved HbA 1c <7% and ≤6.5%, compared with 36% and 23% on unchanged GLP-1RA, respectively. Fasting plasma glucose and 9-point self-monitored blood glucose profiles improved significantly more with IDegLira versus unchanged GLP-1RA. The mean change in weight was +2.0 kg with IDegLira, versus −0.8 kg with unchanged GLP-1RA. Rates of confirmed hypoglycemia were low, but higher with IDegLira versus unchanged GLP-1RA. The safety profile of IDegLira was consistent with previous findings; both treatments were well tolerated and the rate of nausea was low in both groups. IDegLira improved patient-reported outcomes versus unchanged GLP-1RA. Conclusions IDegLira provided superior glycemic control versus unchanged GLP-1RA and represents an efficacious intensification approach in patients inadequately controlled on GLP-1RAs. Trial registration ClinicalTrials.gov #NCT01676116. Funding Novo Nordisk.

Objectives IDegLira is a novel fixed-ratio soluble combination of insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide approved for type 2 diabetes (T2D) patients. Individual trials have assessed the clinical profile of IDegLira vs different comparators. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of IDegLira for T2D. Methods PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched from inception to August 15, 2023. The primary outcomes included change from baseline in haemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. Results This meta-analysis identified 1044 citations, and included 13 eligible trials, enroling 7773 patients. Compared with the control groups, IDegLira was optimal in change in HbA1c, percentage of patients achieving HbA1c < 7%, percentage of patients achieving HbA1c < 6.5%, HbA1c < 7.0% without weight gain and without severe or blood glucose (BG)-confirmed hypoglycaemia episodes, HbA1c < 6.5% without weight gain and without severe or BG-confirmed hypoglycaemia episodes, change in fasting plasma glucose, change in self-measured plasma glucose, change in systolic pressure, and total daily insulin dose. No difference was found between the IDegLira and control groups in terms of change in body weight, change in diastolic pressure, severe or BG-confirmed symptomatic hypoglycaemia, nocturnal severe or BG-confirmed symptomatic hypoglycaemia, adverse events or serious adverse events. Conclusions In patients with T2D, IDegLira improved glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.

This communication provides a contemporary classification of glucagon-like peptide 1 receptor agonists (GLP1RAs) based on indication, route, and frequency of administration, which could support a person-centric approach to treatment choice. It includes all recently developed GLP1RAs as well as those in advanced stages of clinical study. Keeping pace with current trends in pharmacology and metabolic medicine, it attempts to bring clarity and simplicity to a complex spread of information.

Introduction This study aimed to evaluate the effectiveness and safety of switching from basal bolus insulin treatment (BBIT) to a fixed combination of insulin degludec and liraglutide (IDegLira) in patients with type 2 diabetes mellitus (T2DM) who had preserved insulin secretion but inadequate glucose control. The study also aimed to assess the feasibility of implementing this therapeutic approach in common clinical practice settings. Methods This was a non-randomized, open-label, multicenter, prospective, single-arm study involving 234 patients with T2DM who were receiving BBIT. Inclusion criteria were duration of diabetes mellitus > 60 months, stable total daily dose of insulin (TDDI) ranging from > 20 to < 70 IU/day (approx. > 0.3 to < 0.7 IU/kg body weight/day), C-peptide levels > 10% above the lower limit, HbA1c levels > 7% and < 10% (Diabetes Control and Complications Trial), and body mass index > 25 kg/m 2 . The primary endpoints were changes in glycated hemoglobin (HbA1c) and body weight at week 28 after treatment switching. Secondary endpoints included changes in the 7-point glycemic profile, hypoglycemia frequency, blood pressure, blood lipids, liver enzymes, insulin dose, and a patient questionnaire focusing on treatment satisfaction, concerns and impact on daily activities. A subgroup of 55 patients underwent continuous glucose monitoring (CGM) with the evaluation of CGM-derived parameters, such as time in range (TIR), time above range (TAR), time below range (TBR), hypoglycemia, and glucose variability. Results A significant decrease in HbA1c (8.6% vs. 7.6%; p  < 0.0001) and body weight (97.8 vs. 94.0 kg; p  < 0.0001) was observed at week 28 after treatment switching. Significant improvements were also seen in all measurements of the 7-point glycemic profile ( p  < 0.0001), reduction in the number of hypoglycemia episodes per patient, and the proportion of patients with at least one hypoglycemia event ( p  < 0.001). Furthermore, there was a significant decrease in daily insulin dose (55.6 vs. 32.7 IU/day; p  < 0.0001), as well as improvements in blood pressure, blood lipids, and liver enzymes (gamma glutamyl transferase and alanine aminotransferase). The subgroup of patients who underwent CGM showed a significant increase in TIR (57.9% vs. 69.0%; p  < 0.01) and a decrease in TAR (40.1% vs. 28.8%; p  < 0.01), while TBR, hypoglycemia (number of episodes per patient and proportion of patients), and glucose variability did not change significantly. Conclusion The results of this study suggest that switching from BBIT to IDegLira in patients with T2DM and preserved insulin secretion can simplify treatment without compromising glycemic control. The switch to IDegLira was associated with significant improvements in various glucose control parameters, including HbA1c, glycemic profile, hypoglycemia, insulin doses, and CGM-derived parameters TIR and TAR. Additionally, it led to significant reductions in body weight, blood pressure, lipid profile, and liver enzyme levels. Switching to IDegLira may be considered a safe and beneficial approach in clinical practice settings, offering metabolic and individual advantages.

Introduction Type 2 diabetic patients suffering from severe hyperglycemia are often assigned a regimen involving multiple daily injections (MDI) of insulin. If the glucose toxicity resolves, the regimen can potentially be simplified, but there are no guidelines for this, and many patients are left on the MDI regimen. We aimed to prospectively examine the safety and efficacy of switching from MDI to once-daily IDegLira, a fixed-ratio combination of insulin degludec and liraglutide, in relatively well controlled (HbA1c ≤ 7.5%) subjects with type 2 diabetes on a low total daily insulin dose (TDD). Methods 62 adults with type 2 diabetes (baseline age 64.06 ± 10.24 years, HbA 1c 6.42 ± 0.68%, BMI 33.53 ± 6.90 kg/m 2 , body weight 93.81 ± 19.26 kg, TDD 43.31 ± 10.99 IU/day, insulin requirement 0.47 ± 0.13 IU/kg, duration of diabetes 10.84 ± 7.50 years, mean ± SD) treated with MDI ± metformin were enrolled in our study. Previous insulins were stopped and once-daily IDegLira was started. IDegLira was titrated by the patients to achieve a self-measured pre-breakfast blood glucose concentration of < 6 mmol/L. Results After a mean follow-up period of 99.2 days, mean HbA 1c had decreased by 0.30% to 6.12 ± 0.65% ( p  < 0.0001), body weight had decreased by 3.11 kg to 90.70 ± 19.12 kg ( p  < 0.0001), and BMI had reduced to 32.39 ± 6.71 kg/m 2 ( p  < 0.0001). After 3 months of treatment, the mean dose of IDegLira was 20.76 ± 6.60 units and the mean insulin requirement had decreased to 0.23 ± 0.08 IU/kg. IDegLira ± metformin combination therapy was found to be safe and generally well tolerated. During the month before the baseline visit, 28 patients (45%) had at least one episode of documented or symptomatic hypoglycemia, while only 6 (9.67%) patients reported a total of 13 documented episodes during the follow-up. Conclusion In everyday clinical practice, switching from low-dose MDI to IDegLira in patients with well-controlled type 2 diabetes is safe, may result in weight loss and similar or better glycemic control, and substantially reduces the insulin requirement. Simplifying complex treatment regimens decreases treatment burden and may improve adherence to therapy. Clinical Trial Number NCT04020445.

Objective: To evaluate the real-world use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in the Pakistani population with type II diabetes (T2D). Methods: This multicenter, retrospective study collected real-world data from various public & private hospitals, and primary care clinics in Pakistan. The total duration of clinical data collection was six months (April and September 2022) from 183 diabetic patients across different centers in Pakistan. Patients who had received IDegLira in combination with basal/premixed insulin, OHAs, or both regimes (basal/premixed insulin and OHAs) for the treatment of Type-II diabetes (T2D) in the Pakistani population were analyzed. Results: After receiving IDegLira therapy for six months, mean HbA1c was reduced by -1.1%, mean body weight reduced by 1.2 kg, fasting blood glucose levels (mg/dl): 164.7 (±36.2) to 134.4 (±32.9)] and random blood sugar (mg/dl): 240.1 (±71.4) to 207.6 (±77.8)]. The mean IDegLira dose steps were 19.9 (±6.7) at initiation and 23.5 (±7.9) at follow-up. Overall, adverse events reported were generally related to gastrointestinal, and few were related to headache, fatigue, and hypoglycemia events. Conclusion: The values of HbA1c and body weight decreased for the patients after using iDeglira for six months. Therefore, the medicine had a positive impact on the outcome of the study. doi: https://doi.org/10.12669/pjms.41.5.11002 How to cite this: Raja UY, Wahab MU, Randhawa FA, Hussain A, Raza A, Mahar SA, et al. Multicenter, Retrospective, observational study to evaluate the real-world use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in the Pakistani population with Type-2 diabetes (T2D). Pak J Med Sci. 2025;41(5):1494-1498. doi: https://doi.org/10.12669/pjms.41.5.11002 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background In 2021, IDegLira was introduced in China as a treatment option for patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the long-term cost-utility of IDegLira compared to basal-bolus therapy and glucagon-like peptide-1 receptor agonist (GLP-1RA) added to basal insulin in patients with T2DM who remain uncontrolled on basal insulin in China. Methods The Swedish Institute for Health Economics (IHE) T2DM Cohort Model was employed to project health and cost outcomes over a 30-year time horizon. Baseline cohort characteristics were derived from the DUAL II China study. Treatment effects were derived from DUAL VII study and a pooled analysis. Costs were considered from a health system perspective in China and expressed in 2023 Chinese yuan (CNY). Health outcomes were measured in quality-adjusted life years (QALYs). Health state utilities were obtained from several published sources. Future costs and clinical outcomes were discounted at an annual rate of 5%. Results IDegLira was associated with an improvement of 0.810 QALYs and a cost reduction of CNY 91,217 compared to basal-bolus therapy. Similarly, compared to GLP-1RA added to basal insulin, IDegLira demonstrated a health gain of 0.011 QALYs and a cost reduction of CNY 23,815, establishing IDegLira as the dominant option. The sensitivity analyses indicated a 100% probability of IDegLira being cost-effective. Conclusions For T2DM patients who remain uncontrolled on basal insulin, IDegLira was projected to be dominant and could offer better value compared to both basal-bolus therapy and GLP-1RA added to basal insulin in the Chinese setting.

Introduction: IDegLira (brand name Xultophy) is a novel fixed ratio combination of insulin degludec and liraglutide for type 2 diabetes (T2D) patients. This study aimed to investigate the lifetime cost-effective value of IDegLira compared with its single component (Degludec or Liraglutide) and to explore the suitable annual cost of IDegLira if necessary. Methods: UKPDS OM2 was applied to determine the long-term quality-adjusted life years (QALYs) and total costs. The efficacy data that were inputted into the model were synthesized from 6 randomized clinical trials (RCTs) that directly assessed the clinical benefit of IDegLira and its components in the treatment of uncontrolled T2D patients. The economic results were examined by one-way sensitivity analysis (OSA) and probabilistic sensitivity analysis (PSA). Further price reduction of IDegLira was investigated by binary search. Results: The IDegLira, IDeg, and Lira yielded 11.79 QALYs, 11.62 QALYs, and 11.73 QALYs and total cost of$20281.61, $ 3726.76, and$11941.26, respectively. The incremental cost-utility ratio (ICUR) of IDegLira versus IDeg was $ 99464.12/QALYs, and the ICUR of IDegLira versus Lira was $143348.26/QALYs, which indicated that IDegLira was not a cost-effective therapy for T2D patients compared with its components at the current price from a Chinese national healthcare system perspective. Base case results were robust to OSA and PSA. A further binary search showed that IDegLira appears to only be cost-effective if the annual cost of IDegLira is decreased by 58% when IDeg is considered as a reference, or by 30.57% when Lira is considered as a reference. Conclusion: In conclusion, IDegLira appears to not be cost-effective when compared with the current prices of IDeg or Lira for T2D patients in China. However, after the binary search, IDegLira appears to only be cost-effective if the annual cost of IDegLira is decreased 58% when IDeg is considered as a reference, or by 30.57% when Lira is considered as a reference.

Introduction Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. Methods We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018–2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. Results Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group ( p  < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. Conclusions Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.

Introduction Fixed ratio combination of insulin degludec and liraglutide (IDegLira) represents an option to revise inappropriate therapies in patients with poorly controlled type 2 diabetes. This study aimed to assess the pattern of use and 1-year effectiveness of IDegLira. Methods A retrospective chart review was performed to assess changes in glycated hemoglobin (HbA1c) (primary endpoint), fasting blood glucose (FBG), body weight, estimated glomerular filtration rate (eGFR), and lipid profile following IDegLira initiation. Previous versus concomitant diabetes treatments were also compared. Results Overall, 87 patients (mean age 73.9 ± 9.2 years, diabetes duration 18.2 ± 6.7 years, 62.1% men, HbA1c 8.3 ± 1.3%, BMI 30.4 ± 5.5 kg/m 2 ) initiated IDegLira. Previously, 21.8% of patients were treated with oral hypoglycemic agents (OHA group), 47.1% with basal insulin ± OHA (BOT group), 5.8% with GLP-1 RA ± basal insulin (GLP1-RA group), and 25.3% with basal-bolus schemes (BB group). At the first prescription of IDegLira, secretagogues and schemes including two or more OHA were substantially reduced, leaving metformin as the most prevalent OHA (81.6%) used in combination with IDegLira. Starting dose of IDegLira ranged from 18.7 ± 3.1 U (OHA group) to 24.1 ± 4.4 U (BB group). After 1 year, HbA1c was significantly reduced by 1.25% (95% CI − 1.48; − 1.03), FBG by 52.9 mg/dl, and body weight by 2.0 kg. Also, eGFR levels and lipid profile significantly improved. No severe hypoglycemia occurred. Conclusion It is possible to proactively review suboptimal or inappropriate diabetes treatment according to the most recent guidelines. Results suggest that initiation of IDegLira was associated with a reduction in drugs to be administered daily and relevant improvements in clinical outcomes.