Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics.

AIM: To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics. METHODS: SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function. RESULTS: No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P > 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P = 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events. CONCLUSIONS: Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.

Switching the basal insulin to insulin glargine 300 U/ml in people with type 2 diabetes under basal insulin supported oral therapy: Observational trial on effectiveness and safety.

AIMS: This study evaluated the effectiveness and safety of switching the basal insulin (BI) in a BI-supported oral therapy (BOT) to insulin glargine 300 U/ml (Gla-300) in adults with inadequately controlled type 2 diabetes (T2D). MATERIALS AND METHODS: This was a non-interventional, multicentre, prospective 12-month study, conducted in Germany, Austria and Switzerland. The study documented people with T2D with glycated haemoglobin (HbA1c) between 7.5% and 10.0%, currently treated by a non-Gla-300 BOT regimen, after the physician had decided to switch the BI to Gla-300. Primary endpoint was the proportion of patients achieving the fasting plasma glucose (FPG; ≤110 mg/dl) target. RESULTS: In total, 1194 participants comprised the full analysis set, of which 793 completed documentation of 12 months Gla-300 treatment (FAS-M12). The main previous BI was insulin glargine 100 U/ml (Gla-100; 47.2%). Twelve months after switching to Gla-300, 27.0% of FAS-M12 participants achieved the FPG target and 44.8% their individualized HbA1c target. The greatest FPG target achievements were seen in previous Gla-100 (29.3%), and greatest HbA1c target achievements in previous insulin detemir users (57.7%). The mean FPG decreased by -36.3 ± 51.2 mg/dl to 135.5 ± 36.9 mg/dl and mean HbA1c by -0.79 ± 1.01% to 7.45 ± 0.94%. Symptomatic and nocturnal hypoglycaemia incidence significantly decreased over 12 months of Gla-300 treatment. Body weight remained unchanged. CONCLUSIONS: Switching the BI to Gla-300 in a BOT regimen improved metabolic control and treatment satisfaction in a substantial proportion of patients with T2D and inadequate target achievement within 12 months in clinical practice with a decreased risk of symptomatic and nocturnal hypoglycaemia and without weight gain.

Effectiveness and safety of insulin glargine 300 U/mL in insulin-naïve patients with type 2 diabetes after failure of oral therapy in a real-world setting.

AIM: To evaluate the effectiveness and safety of initiating basal insulin-supported oral therapy (BOT) with insulin glargine 300 U/mL (Gla-300) in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs (OADs). MATERIALS AND METHODS: This non-interventional, multi-centre, prospective 52-week study, conducted in Germany and Switzerland, documented patients with type 2 diabetes with an HbA1c of between 7.5% and 10.0%, currently treated with OADs, after the physician had decided to start a BOT regimen with Gla-300. The primary endpoint was the rate of achievement of the individualized predefined HbA1c target. RESULTS: Of 1748 patients included, 1153 comprised the full analysis set, of whom 721 completed documentation of 12 months of Gla-300 treatment. Twelve months after starting Gla-300, 49.9% achieved their individualized HbA1c target, and 61.1% achieved either their HbA1c target or a fasting plasma glucose (FPG) of ≤110 mg/dL. Mean HbA1c decreased by -1.22% ± 1.05% to 7.28% ± 0.92% and mean FPG by -51.5 (±48.63) mg/dl to 132.9 ± 33.0 mg/dL. Median duration of HbA1c target achievement was 341 days and probability to remain on target after 6 months was 81%. Hypoglycaemia incidence and rates remained low after 12 months of Gla-300 treatment; no severe or severe nocturnal hypoglycaemia was observed. Body weight remained unchanged. CONCLUSIONS: Starting a BOT regimen with Gla-300 allowed about 60% of 721 German and Swiss patients with inadequately controlled type 2 diabetes to achieve glycaemic control within 12 months in daily clinical practice. Glycaemic control was achieved without weight gain or increased risk of nocturnal or severe hypoglycaemia.

Titration of insulin glargine 100 U/mL when added to oral antidiabetic drugs in patients with type 2 diabetes: results of the TOP-1 real-world study.

AIMS: Adequate insulin titration is crucial for optimal glycaemic control in type 2 diabetes (T2D). We aimed to explore the factors and outcomes associated with titration of glargine 100 U/mL (Gla-100) in patients uncontrolled on oral antidiabetic drugs (OAD) and initiating insulin therapy. METHODS: Patients from the Titration and Optimization (TOP)-1 registry were stratified by the magnitude of Gla-100 up-titration during the first month (no [< 1 Units (U)/day (d)], minimal [≥ 1 and < 5 U/d], moderate [≥ 5 and ≤ 8 U/d] and strong [> 8 U/d]). The primary endpoint was a fasting blood glucose (FBG) ≤ 110 mg/dL on ≥ 2 occasions and/or individual HbA1c target by 12 months. RESULTS: Of 2308 patients, 905, 715, 409 and 279 underwent no, minimal, moderate and strong titration, respectively. Age decreased across increasing titration groups (p = 0.02) while body mass index (BMI) (p < 0.0001), FBG (p < 0.0001), and HbA1c (p < 0.0001) increased. At 12 months, the proportions of patients achieving the primary endpoint were comparable across groups (66.1% overall), though a smaller proportion of no titration patients met both their individual HbA1c target and FBG ≤ 110 mg/dL compared to moderate and strong titration patients (20.1% vs. 27.2% and 26.2%, p = 0.033 and 0.023, respectively). HbA1c was also comparable, though FBG was higher in the no titration group (126.2 vs. 122.6, 121.5 and 120.9 mg/dL, p < 0.02). A similar, small reduction in body weight occurred in all groups; hypoglycaemia rates were comparable across groups. CONCLUSIONS: In real-world, titration of Gla-100 during the first month appears to coincide with a number of baseline factors. Insulin dose to meet HbA1c and FBG targets remains suboptimal in the majority of T2D patients.

HbA1c target achievement in the elderly: results of the Titration and Optimization trial for initiation of insulin glargine 100 U/mL in patients with type 2 diabetes poorly controlled on oral antidiabetic drugs.

Objectives: To identify real-world, age-related trends in the use of insulin glargine 100 U/mL (Gla-100) as part of basal-supported oral therapy (BOT). Research design and methods: The prospective, observational Titration and Optimization registry enrolled patients with poorly controlled type 2 diabetes mellitus initiated on Gla-100 BOT. The primary outcome was the proportion of patients with capillary fasting blood glucose (FBG) ≤110 mg/dL on ≥2 occasions and/or who met their individual HbA1c target within 12 months. Results: 2462 patients were analyzed (<65 years: n=1122; 65-74 years: n=771; ≥75 years: n=569). Diabetes duration (6.8, 8.9, and 11.2 years, p<0.0001) and proportion of women (40.7%, 47.9%, and 55.7%, p<0.0001) increased with age. Baseline HbA1c was highest in <65-year-olds (8.6% vs 8.4% and 8.5%, p<0.0001). Gla-100 up-titration until 12 months was highest in <65-year-olds (+11.6 U/day), compared with 65-74 (+10.2 U/day) and ≥75 years (+8.8; p<0.0001) but similar by units per kilogram, as was the decrease in FBG (<65: -64.1 mg/dL; 65-74: -56.1 mg/dL; ≥75: -53.4 mg/dL) and HbA1c (<65: -1.47%; 65-74: -1.31%; ≥75: -1.22%, p<0.0001). At 12 months, 65.9% of participants met the primary endpoint, with no significant difference between age groups. The proportion achieving their individual HbA1c target was lower for <65-year-olds (46.0% vs 54.3% and 54.7%; p<0.02). Symptomatic hypoglycemia incidence was more common in the ≥75-year-old group (3.4% vs 1.4% and 1.4%; p=0.0126). Conclusions: BOT with Gla-100 results in similar improvements of glycemic values with low risk of hypoglycemia across age groups. Given the link between HbA1c and long-term cardiovascular risk, ensuring appropriately stringent target-setting, intensification of basal insulin and making sure hypoglycemia is avoided is of paramount importance. Trial registration number: Database: https://awbdb.bfarm.de; Identifier: 1641; Date of registration: September 23, 2013.

Predictors of treatment response in type-2 diabetes patients initiating basal-supported oral therapy with insulin glargine 100 U/mL: A sub-analysis of the Titration and OPtimisation (TOP) registry.

The aim of this study was to identify predictors of long-term response to the initiation of basal-supported oral therapy (BOT) with insulin glargine (IGlar-100). Patients from the observational TOP registry were grouped based on those who had achieved (responders) and those who had not achieved (non-responders) their HBA1c target and/or FBG ≤110 mg/dL 12 months after IGlar-100 initiation. Independent predictors of treatment response were identified by regression analysis. Data for 2444 patients were analysed (responders, n = 1610; non-responders, n = 834). Although the IGlar-100 dose increase over 12 months was larger for non-responders (+12.83 vs +9.46 U/d; P < 0.0001), the corresponding decrease in HbA1c was smaller (-0.88% vs -1.57%). Independent predictors of response included lower BMI (OR, 0.97; 95% CI, 0.95-1.00), lower FBG (OR, 0.98; 95% CI, 0.97-0.98) and HbA1c values at baseline (OR, 0.24; 95% CI, 0.18-0.31), a less ambitious HbA1c target (OR, 5.07; 95% CI, 3.37-7.63) and bedtime administration of IGlar-100 (OR, 1.55; 95% CI, 1.12-2.14). In conclusion, HbA1c was the clinically most significant baseline characteristic predictive of response to BOT. This may suggest an advantage of IGlar-100 initiation prior to excessive hyperglycaemia escalation.

Titration and optimization trial for the initiation of insulin glargine 100 U/mL in patients with inadequately controlled type 2 diabetes on oral antidiabetic drugs.

For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, addition of basal insulin is recommended, but titration and optimization of basal insulin therapy in primary care is not well understood. We conducted an observational trial in 2470 patients with T2DM who initiated insulin glargine 100 U/L (Gla-100) on top of oral antidiabetic drugs. Physicians were free to choose either a "Davies," "Fritsche" or "individual" titration algorithm. We found that fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) levels were effectively reduced by Gla-100; 65.9% of patients achieved the primary endpoint (FBG ≤6.1 mmol/L (110 mg/dL) or an individual HbA1c target). There were no significant differences in efficacy and safety between the algorithms used. The mean FBG decreased by 3.2 mmol/L (59 mg/dL) over 12 months, while the mean HbA1c decreased by 15.3 mmol/mol (1.4%)%. From a starting dose of 11.7 U/d, the Gla-100 dosage was 22.8 U/d at 12 months, with similar values in each group. Rates of hypoglycaemia were low and did not differ by titration algorithm. We conclude that Gla-100 was effective at reducing FBG and HbA1c, independent of the titration algorithm, but observed that algorithms were inconsistently applied in clinical practice.

Effectiveness and tolerability of treatment intensification to basal-bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study.

BACKGROUND: Due to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3-6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal-bolus therapy (BBT) regimen in T2DM patients in daily clinical practice. METHODS: This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT). RESULTS: A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m(2); pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean -0.94% and -0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean -1.29% and -1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1). CONCLUSION: Intensifying glargine-based BOT or glulisine-based SIT to a BBT regimen in poorly controlled T2DM patients in daily routine care led to marked improvements of glycemic control and was well tolerated.

Efficacy and safety of insulin glargine added to a fixed-dose combination of metformin and a dipeptidyl peptidase-4 inhibitor: results of the GOLD observational study.

BACKGROUND: For patients with type 2 diabetes who are uncontrolled on a combination of two oral antidiabetic agents, addition of the long-acting basal insulin glargine is a well established treatment option. However, data on the efficacy and safety of a combination of metformin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin glargine are limited in real-world settings. Therefore, the aim of this study was to analyze blood glucose control, rates of hypoglycemia and body weight in a large cohort of patients with type 2 diabetes treated with this combination therapy in real practice. METHODS: This noninterventional, multicenter, prospective, observational trial with a follow-up of 20 weeks enrolled insulin-naïve patients who had been on a stable fixed dose of metformin and a DPP-4 inhibitor for at least 3 months, and had a glycosylated hemoglobin (HbA1c) between 7.5% and 10%. Patients were selected at the investigators' discretion for initiation of insulin glargine at baseline. A total of 1,483 patients were included, of whom 1,262 were considered to be the efficacy set. Primary efficacy parameters were HbA1c and fasting plasma glucose. Secondary outcome measures included achievement of glycemic targets, body weight, rates of hypoglycemia, and other safety parameters, as well as resource consumption. RESULTS: Upon initiation of insulin glargine, mean HbA1c decreased from 8.51% to 7.36% (-1.15%±0.91%; 95% confidence interval [CI] -1.20 to -1.10). An HbA1c level<6.5% was achieved in 8.2% of patients and a level<7.0% in 31.5%. Mean fasting plasma glucose decreased from 174±47 mg/dL to 127±31 mg/dL (-47.3±44.1 mg/dL; 95% CI -49.8 to -44.8). In 11.9% of patients, a fasting plasma glucose level<100 mg/dL was achieved. Bodyweight decreased on average by 0.98±3.90 kg (95% CI 1.19-0.76). Hypoglycemia (blood glucose≤70 mg/dL) was observed in 29 patients (2.30%), of whom six (0.48%) had nocturnal hypoglycemia and four (0.32%) had documented severe events (blood glucose<56 mg/dL). CONCLUSION: The results of this observational study show that insulin glargine, when added to a fixed-dose combination of metformin and a DPP-4 inhibitor, resulted in a significant and clinically relevant improvement of glycemic control. Importantly, this intervention did not interfere with the action of the DPP-4 inhibitors, resulting in neutral effects on weight and low rates of hypoglycemia. We conclude that this treatment intensification approach may be useful, efficient, and safe in daily clinical practice for patients with type 2 diabetes.