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.

Preulcerous Risk Situation in Diabetic Foot Syndrome: Proposal for a Simple Ulcer Prevention Score.

BACKGROUND: Preulcerous risk situations in patients with diabetes are often undiagnosed and care administered too late. Even with regular medical check-ups and status documentation, foot examinations have not been given enough attention. Diagnosing an individual patients' risk of developing diabetic foot ulcers may increase vigilance for diabetic foot syndrome (DFS), and the appropriate prevention measures matching the risk involved may prevent the emergence of diabetic ulcers. The classical DFS risk factors are well established and have been extensively covered in the literature; however, there is a lack of efficient screening tools that could be used for a rapid assessment of diabetic foot ulcer risk. METHODS: A methodical literature search was conducted to assess relevant publications for the preparation of a simple risk score for amputation related to diabetic foot ulcer. We then analyzed the risk factors for predictive value as odds ratios in foot ulcers and/or amputation. We used the available data to deduce a mean value to reflect the authors' consensus. RESULTS: In view of the current literature on the matter, we have developed a semi-quantitative scoring system using just a few items to allow rapid and visual risk assessment for diabetic foot ulcers alongside recommendations for prevention and a sensible follow-up strategy to match the risk. CONCLUSION: This relatively simple score enables rapid risk classification for patients that can ease the way for both physicians and patients in gaining an insight into individual risk situations. The score provides more effective preventative measures for high-risk patients against future complications.

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.

Early discontinuation and related treatment costs after initiation of Basal insulin in type 2 diabetes patients: a German primary care database analysis.

AIMS: The aim was to compare early discontinuation and related treatment costs in type 2 diabetes in primary care after initiation of insulin glargine or human basal insulin (NPH). METHODS: Overall, 2765 glargine and 1554 NPH patients from 1072 general practices were analyzed (Disease Analyser). Early discontinuation was defined as switching to a different basal insulin or another insulin treatment regimen within 90 days after first basal insulin prescription (index date, ID). Treatment costs were assessed 365 days prior and post ID in both groups. Propensity score matching and linear regression was used to adjust cost differences (post vs prior ID: discontinued vs continued patients) for age, sex, diabetes duration, antidiabetic comedication, diabetologist care, disease management program participation, costs before ID, and Charlson Comorbidity Index. RESULTS: Within 3 months after ID, 13% of glargine patients switched to other insulin treatment regimens (NPH: 18%; P < .05). After propensity score matching, adjusted cost differences in 146 discontinued versus 1342 continued glargine patients were calculated (NPH: 146 vs 1342). Diabetes-related prescription costs were lower among persistent glargine patients compared to persistent NPH patients (EUR-49 [19]; P = .0109). Mean cost difference for diabetes-related prescriptions was lower among those who persisted on glargine compared to those who switched to other treatment regimens (EUR-74 [42], P = .0780). CONCLUSIONS: Treatment persistence within 3 months after basal insulin initiation was significantly higher under insulin glargine compared to NPH. Diabetes-related prescription costs were significantly lower among patients who adhered to insulin glargine compared to persistent NPH patients.