Initiating Insulin Glargine Research Articles

THU388 Insulin Edema Associated With Glargine: A Case Report And Brief Review Of Literature

Abstract Disclosure: J. Wood: None. V. Samji: None. F.S. Celi: None. P. Majety: None. Introduction: Insulin edema is an uncommon and poorly understood complication of insulin therapy in patients with diabetes. We report a patient with type 1 diabetes (T1DM) who developed edema within days of initiating insulin glargine that resolved with discontinuation of this medication. Case Report: A 20-year-old man with no past medical history presented with nausea, vomiting, polydipsia, and a 15-pound weight loss and was noted to have a hemoglobin A1c greater than 14.0%. Diabetic ketoacidosis (DKA) was ruled out and was started on weight-based insulin therapy with glargine and lispro three units with meals. Additional diabetes workup was notable for positive Anti-IA2 antibodies. Blood glucose levels improved prior to discharge. A week after discharge, he complained of swelling of limbs. Patient denied any shortness of breath, cough, chest pain, orthopnea, or nocturnal dyspnea. He was found to have extensive 2+ pitting edema in bilateral feet extending up to his calves. Dorsalis Pedis pulses were 2+ bilaterally. No warmth or erythema of legs was noted. His weight in clinic was 70.2 kg (154.4 lbs), up 11.6 kg (25.5 lbs) ten days post discharge. Evaluation for bilateral pedal edema was performed. Labs were notable for normal liver enzymes, creatinine, glomerular filtration rate and urine albumin levels, ruling out hepatic and renal causes of edema. Thyroid function tests were normal. His presentation was discussed with cardiology and brain natriuretic peptide level was drawn which was also normal. No further cardiac workup was recommended at that time given the patient’s history and lack of other clinical signs or symptoms of heart failure. After ruling out other systemic causes of edema in our patient, a diagnosis of insulin edema was made. Based on prior case reports of glargine associated insulin edema, he was switched from insulin glargine to insulin degludec. He noted significant improvement within 24 hours of switching insulin with a 6.4-pound weight loss in just one day and complete resolution of edema within 3 days. He had no recurrence of edema once glargine was discontinued despite increasing insulin dosing for glycemic control. Conclusion: The pathophysiology of insulin edema is unclear. Insulin’s role in renal sodium handling, vasodilation, and increased vascular permeability, have been postulated as possible mechanisms. Risk factors for developing insulin edema include T1DM, high A1C, high dose of insulin, rapid correction of hyperglycemia, DKA on presentation and poor nutritional status. Additional risk factors for developing insulin edema include thiamine deficiency and an underlying genetic predisposition related to a mitochondrial mutation, although this seems to be rare. Insulin edema is a diagnosis of exclusion. Clinicians should be aware of this rare complication, and its occurrence should be documented and differentiated from other causes of edema. Presentation: Thursday, June 15, 2023

Fasting Glucose of 6.1 mmol/L as a Possible Optimal Target for Type 2 Diabetic Patients with Insulin Glargine: A Randomized Clinical Trial.

To observe whether different insulin glargine titration algorithms based on fasting blood glucose (FBG) levels lead to different glycaemic variations (GVs) in type 2 diabetes (T2D) patients, a prospective, randomized, single-centre, comparative, three-arm parallel-group, open-label, treat-to-target, 24-week study was performed. A total of 71 uncontrolled T2D patients were recruited and randomized 1 : 3 : 3 into Groups 1, 2, and 3 (insulin titration goals of FBG ≤ 5.6, ≤6.1, and ≤7.0) for this study. The initiated insulin glargine dose was recommended at 0.2 U/kg/day and was then titrated following the FBG target. Patients were subjected to two 3-day continuous glucose monitoring (CGM) at baseline and the endpoint, wherein the CGM data were analysed, and the study's primary endpoint was the difference in 24 hrs mean amplitude of glycaemic excursion (MAGE) among the three groups. We observed that patients in the three groups had similar MAGE levels at the endpoint; however, Group 2 achieved a significant decrease in the MAGE level from baseline to the endpoint as compared to Groups 1 and 3 (all p < 0.05). We also observed that these patients had significant glycated haemoglobin A1c (HbA1c) value improvements as compared to the other two groups (all p < 0.05). Therefore, choosing an FBG level of 6.1 mmol/L as an insulin titration target provided significant GVs and HbA1c value improvements in T2D patients. Moreover, our data indicated that an FBG of 6.1 mmol/L could possibly be an insulin glargine titration target in T2D patients.

Severe Hypoglycemia Risk With Long-Acting Insulin Analogs vs Neutral Protamine Hagedorn Insulin

Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use. To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings. This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019. Insulin glargine, insulin detemir, and NPH insulin. The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age. Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use. In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

65 - Randomized Comparison of Initiating Insulin Glargine or Iglarlixi in South Asian Canadians With Type 2 Diabetes: VARIATION 2 SA Trial

To compare initiation of a fixed-ratio combination of glargine-lixisenatide (iGlarLixi) and insulin glargine U100 (iGlar), exclusively in South Asian origin Canadians.

Similar Breast Cancer Risk in Women Older Than 65 Years Initiating Glargine, Detemir, and NPH Insulins.

To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes. This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388) from September 2006 to September 2015, with follow-up through May 2017. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for incidence of breast cancer according to ever use, cumulative duration of use, cumulative dose of insulin, length of follow-up time, and a combination of dose and length of follow-up time. Ever use of glargine was not associated with an increased risk of breast cancer compared with NPH (HR 0.97; 95% CI 0.88-1.06) or detemir (HR 0.98; 95% CI 0.92-1.05). No increased risk was seen with glargine use compared with either NPH or detemir by duration of insulin use, length of follow-up, or cumulative dose of insulin. No increased risk of breast cancer was observed in medium- or high-dose glargine users compared with low-dose users. Overall, glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir in female Medicare beneficiaries.

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

ObjectivesTo 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 methodsThe prospective, observational Titration and Optimization registry...

Comparable glycaemic control and hypoglycaemia in adults with type 2 diabetes after initiating insulin glargine 300 units/mL or insulin degludec: The DELIVER Naïve D real-world study.

AimTo compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla‐300) and insulin degludec (IDeg) in a real‐world study of insulin‐naïve adults with type 2 diabetes (T2D).Materials and methodsDELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin‐naïve adults with T2D who started Gla‐300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla‐300 or IDeg and had HbA1c measurements during 6‐month baseline and 3‐ to 6‐month follow‐up. Outcomes were compared among 1:1 propensity score‐matched cohorts.ResultsIn the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla‐300 and IDeg cohorts (−1.67% [2.22] and −1.58% [2.20]; P = 0.51), as were HbA1c target attainment [<7% (53 mmol/mol): 23.8% and 27.4%; P = 0.20; <8% (64 mmol/mol): 55.0% and 57.1%; P = 0.63] and treatment discontinuation (29.2% and 32.6%; P = 0.14). Overall and inpatient/emergency department‐associated hypoglycaemia incidences and event rates were similar in both cohorts using fixed 6‐month or variable on‐treatment follow‐up.ConclusionsAmong real‐world insulin‐naïve adults with T2D, initiation of Gla‐300 or IDeg resulted in comparable improvements in glycaemic control and similar rates of hypoglycaemia. These real‐world data complement and confirm a randomized trial and other real‐world studies.

1109-P: Type 2 Diabetes Treatment in Patients with Chronic Kidney Disease: Efficacy and Safety of Initiating Insulin Glargine 300 U/mL—REALI Pooled Data Analysis

Chronic kidney disease is common in patients with type 2 diabetes (T2D) and has an impact on the choice and dosage of T2D therapies, as well as on the individual’s glycemic target and the risk of hypoglycemia. We evaluated the impact of initiating insulin glargine 300 U/mL (Gla-300) in patients with T2D according to eGFR level, using the REALI pooled database which includes several Gla-300 studies conducted in different European countries. Pooled efficacy and safety analysis of data from three interventional studies was performed on patients treated with Gla-300 having an eGFR at baseline either ≥60 (n=923) or &amp;lt;60 mL/min/1.73m² (n=146). Patients in &amp;lt;60 mL/min/1.73m² group were older (mean age 69.6 vs. 62.9 years), had a longer duration of diabetes (median 14.0 vs. 11.0 years), were more frequently pretreated with basal insulin (54.2% vs. 47.3%), and by insulin glargine 100 U/mL (59.0% vs. 54.8%), than in the ≥60 mL/min/1.73m² group. Higher numbers of previous ischemic events and diabetic complications were also identified in patients with an eGFR at baseline &amp;lt;60 mL/min/1.73m². Mean (SD) HbA1c (%) at baseline was 8.44 (0.82) in the &amp;lt;60 mL/min/1.73m² group and 8.55 (0.87) in the ≥60 mL/min/1.73m² group. The least square mean [95% confidence interval] change from baseline to Week 24 of Gla-300 treatment was -0.79 [-0.96; -0.63] and -1.01 [-1.08; -0.95], respectively. The proportion of patients reaching target HbA1c &amp;lt;7% at Week 24 was 23.4% vs. 30.2%, respectively. There were no differences during on-treatment period between the two groups in symptomatic, severe or nocturnal hypoglycemia rates, as well as in the changes in Gla-300 dose (U/kg/day) and in body weight from baseline to Week 24. This pooled data analysis identifies that patients with T2D and reduced kidney function achieve a clinically important improvement in glycemic control, with no safety concerns, at initiation of treatment with insulin glargine 300 U/mL. Disclosure D. Mauricio: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Sanofi. Speaker's Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. P. Gourdy: Advisory Panel; Self; AstraZeneca. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Speaker's Bureau; Self; Abbott, Amgen Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Sanofi. G. Bigot: None. C. Mauquoi: None. A. Ciocca: Employee; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Funding Sanofi

1097-P: Glycemic Control and Safety Profile of Insulin Glargine 300 U/mL in Older Adults—REALI Pooled Data Analysis

Despite an increasing number of patients with type 2 diabetes (T2D) in the older population, clinical evidence for different therapeutic strategies in the elderly is poor. Therefore, we used the REALI pooled database, which includes a large number of studies conducted in different European countries to evaluate the impact of initiating insulin glargine 300 U/mL (Gla-300) in older patients with T2D. Pooled efficacy and safety analyses of data from three interventional and five observational studies (pooled treated patients, n=5806) were performed on three age groups of patients: &amp;lt;65 (n=2874), 65 to &amp;lt;75 (n=1819), and ≥75 years old (y.o.) (n=1105); age data were missing for 8 patients. The proportion of females, median diabetes duration at baseline and prior use of insulin glargine 100 U/mL increased with age, whereas mean body weight and mean eGFR at baseline decreased with age. Diabetes complications and/or concomitant cardiovascular diseases and risk factors were more frequent in patients ≥75 y.o. Mean (SD) HbA1c (%) at baseline was 8.61 (1.08), 8.42 (0.95), and 8.39 (0.94) in the &amp;lt;65, 65 to &amp;lt;75, and ≥75 y.o. age groups, respectively. The least square mean [95% confidence interval] HbA1c change from baseline to Week 24 of Gla-300 treatment was -0.87 [-0.93; -0.82], -0.83 [-0.89; -0.77] and -0.77 [-0.88; -0.67], respectively. Similar proportions of patients reached the HbA1c &amp;lt;7% and &amp;lt;7.5% goals at Week 24 across the three age groups, with no notable differences between the age groups in incidence of severe (0.7%, 1.2% and 1.2% respectively) and nocturnal (3.1%, 3.6% and 1.7% respectively) hypoglycemia, or mean change in body weight and Gla-300 dose (U/Kg/day) from baseline to Week 24. Gla-300 was well tolerated across all age groups. This pooled data analysis shows that initiation of treatment with insulin glargine 300 U/mL in older (≥ 75 y.o) patients with T2D has a similar efficacy and safety profile as in younger adults, and extends the evidence on treatment of older patients. Disclosure R.C. Bonadonna: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Sanofi-Aventis. D. Mauricio: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Sanofi. Speaker's Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Sanofi. G. Bigot: None. C. Mauquoi: None. A. Ciocca: Employee; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. P. Gourdy: Advisory Panel; Self; AstraZeneca. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Speaker's Bureau; Self; Abbott, Amgen Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis, Servier. Funding Sanofi

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real-world results from the DELIVER Naïve cohort study.

AimsTo compare HbA1c and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla‐300) or 100 units/mL (Gla‐100).Materials and methodsThis retrospective cohort study examined electronic medical records of insulin‐naïve adults with T2D who initiated Gla‐300 or Gla‐100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6‐month baseline and 90–180‐day follow‐up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score‐matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria.ResultsThe matched cohorts included 1004 Gla‐300 and 2008 Gla‐100 initiators (mean age 60.4 years; 53.2% male). During 6‐month follow‐up, Gla‐300 versus Gla‐100 initiators had a greater mean HbA1c decrease (−1.52 ± 2.08% vs. –1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla‐300 initiators were similarly or less likely to have any or inpatient/emergency department‐associated hypoglycaemia during 3‐ and 6‐month follow‐up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057).ConclusionsAmong insulin‐naïve adults with T2D, Gla‐300 was associated with significantly better HbA1c reductions (latest value during 90–180‐day follow‐up) and similar or improved hypoglycaemia outcomes (3‐ and 6‐month follow‐up) than Gla‐100.

Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT-I Study.

AimsTo compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine.Materials and methodsEligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase‐4 (DPP‐4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP‐4 inhibitors and sulphonylureas) and stabilized during a run‐in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L.ResultsA total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and −20.5 mmol/mol (−1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and −15.5 mmol/mol (−1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was −5.0 mmol/mol (−0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups.ConclusionWhen initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.

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.

Effect of Telephone-Delivered Interventions on Glycemic Control in Type 2 Diabetes Treated with Glargine Insulin.

Background:Telephone-delivered intervention can provide support in diabetes self-management to improve glycemic control. "eStar® program" is a telephone support platform for type 2 diabetes on glargine insulin treatment. Its objective is to help patients to perform insulin titration to reach target fasting blood glucose levels. Patients are contacted by trained nurses on a regular basis to adjust the basal insulin dose and reinforce the diabetes education. This study aimed to evaluate if eStar program was effective in helping patients reach their optimal insulin glargine dose within 6 months.Materials and Methods:An observational prospective study was conducted with type 2 diabetes patients who were initiating insulin glargine or requiring dose titration and were eligible to be included in the eStar program. Those participants who followed the program comprised the intervention group, while those who discontinued, the control group. The primary outcome was to evaluate if this program was effective in helping patients reach their optimal insulin glargine dose within 6 months. Secondary outcomes included changes in glycosylated hemoglobin (HbA1C), fasting plasma glucose (FPG), insulin dose, and body mass index after 6 months.Results:A total of 228 subjects [intervention group, 143 (62.7%); control group, 85 (37.3%)] were included in the study. A significantly greater percentage of patients in the intervention group reached their optimal glargine dose than in the control group (83.8% vs. 31.5%; p < 0.001). After 6 months, significant reductions in mean HbA1C levels were observed in both groups: 1.49% (p < 0.001) for the intervention group and 1.08% (p < 0.001) for the control group. Furthermore, a mean reduction in FPG between group was achieved (34.96 mg/dL; p < 0.001).Conclusions:The eStar program is an effective way to help patients reach their optimal insulin glargine dose, besides improving their glycemic control.

Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin.

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla‐100) or insulin detemir (DET) with ≥1 A1C measurement during 12‐month baseline and 18‐month follow‐up periods were included. Patients with a refill gap of >90 days were considered non‐persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow‐up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non‐persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised controlled trials

AimsTo compare outcomes between Asian and non-Asian patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs) initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled clinical trials. MethodsPost hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials. ResultsAt baseline, Asian patients were younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from baseline (7.4% vs. 7.2%; −1.3% vs. −1.6%, respectively; P = .0001), and were less likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients. Reductions in FPG and rates of hypoglycaemia were similar between Asian and non-Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3 vs. +1.9 kg, respectively, P = .013). ConclusionsIn our post hoc meta-analysis, Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled on OADs with similar incidence of hypoglycaemia and less absolute weight gain compared with non-Asian patients. At a similar FPG reduction, fewer Asian patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to be addressed.

Real-world Health Outcomes in Patients with T2D Initiating Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in a Specialist Endocrinology Practice

Real-world Health Outcomes in Patients with T2D Initiating Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in a Specialist Endocrinology Practice

Does hypoglycaemia affect the improvement in QoL after the transition to insulin in people with type 2 diabetes?

PurposeQuality of Life (QoL) of insulin-naïve people with type 2 diabetes mellitus (T2DM) improves after transition to insulin. Little is known about the role of hypoglycaemia in this context. Secondary analyses of the Study of the Psychological Impact in Real care of Initiating insulin glargine Treatment (SPIRIT) aimed to investigate the relationship between hypoglycaemia and QoL when transitioning to insulin.MethodsInsulin-naïve Dutch people with T2DM in suboptimal glycaemic control (HbA1c >53 mmol/mol; 7.0%) on maximum dose of oral glucose-lowering medications were included from 363 primary care practices (n = 911). Participants started insulin glargine and completed QoL-questionnaires (WHO-5 Well-being Index (WHO-5; emotional well-being), Hypoglycaemia Fear Survey-worry scale (HFS-w; hypoglycaemia fear) and Diabetes Symptom Checklist-revised (DSC-r; diabetes symptom distress) at baseline, 3 and 6 months follow-up. Linear GEE analyses were used to investigate the association between symptomatic, nocturnal, severe hypoglycaemia (number of episodes during 3 months prior to visit) and QoL over time.Results52.5% men participated, mean age 62.2 years (SD ± 10.92), and median HbA1c 67 mmol/mol (range 61–77) (8.3%). More symptomatic hypoglycaemic episodes were associated with higher HFS-w and DSC-r scores (P < 0.01). Experiencing multiple nocturnal or severe episodes was related to higher symptom distress as well, when compared to no episodes. These associations did not change significantly over time.ConclusionsHypoglycaemia is associated with lower QoL in terms of hypoglycaemia fear and diabetes symptom distress. The transition to insulin does not affect this relationship, suggesting hypoglycaemia in itself has a detrimental effect on diabetes-related QoL independent of treatment regimen.

Effects of age, gender, and body mass index on efficacy and hypoglycaemia outcomes across treat-to-target trials with insulin glargine 100 U/mL added to oral antidiabetes agents in type 2 diabetes.

To analyse the effects of patient characteristics and different oral antidiabetes drug (OAD) use on standardised clinical outcomes in type 2 diabetes patients initiating insulin glargine 100 U/mL (Gla-100). Patient-level data from 16 randomized, treat-to-target clinical trials that added Gla-100 to existing metformin (MET), sulfonylurea (SU) or metformin plus sulfonylurea (MET+SU) treatment in insulin-naïve patients inadequately controlled by oral therapy were analysed and patients were followed for ≥24 weeks. Change in glycated haemoglobin A1c (HbA1c) from baseline to week 24, other glycaemic endpoints and incidence of hypoglycaemia (overall, nocturnal, and severe) were analysed by age (<65 vs ≥65 years), gender (male vs female), body mass index (BMI; <25 vs ≥25 to <30 vs >30 kg/m2 ) and concomitant OAD (MET vs SU vs MET+SU). At baseline, the overall population (N = 3188) had a mean age of 57.7 years, BMI of 30.5 kg/m2 , HbA1c of 8.7%, fasting plasma glucose of 192 mg/dL, and 52.7% were male. Younger and older patients had similar HbA1c reductions with Gla-100 and a similar risk of hypoglycaemia. Females and patients with BMI <25 kg/m2 were less likely to achieve HbA1c targets and more likely to experience hypoglycaemia, regardless of concomitant OAD. Adding Gla-100 to SU therapy (alone or in combination with MET) increased hypoglycaemia risk across all analyses. Our data suggest that female patients with type 2 diabetes and normal-weight patients treated with Gla-100 and MET ± SU are less likely to achieve glycaemic targets and, therefore, may require more clinical attention. Addition of Gla-100 to SU regimens may increase hypoglycaemia risk irrespective of age, gender, or BMI.

Initiation of insulin glargine plus oral antidiabetic drugs in patients with type 2 diabetes uncontrolled on premixed insulin

Glycaemic control is fundamental in the management of diabetes. The primary objective of this study was to evaluate the effectiveness of insulin glargine administered in combination with oral antidiabetic drugs (OADs) in patients with type 2 diabetes mellitus (T2DM) uncontrolled on pre-mixed insulin-based therapy in the United Arab Emirates, Oman and Kuwait. The secondary objectives were to observe the proportion of patients achieving the targeted glycated haemoglobin (HbA1c) level of < 7% and to describe the safety profile. In this 16-week non-interventional, prospective, multicentre, non-comparative, post-authorization study, we included adults with T2DM who failed to achieve HbA1c < 7% after 3–12 months on pre-mixed insulin-based therapy and whose physician had decided (at his or her discretion) to switch the patient's treatment to basal insulin plus OADs with insulin glargine (one injection), or a basal insulin plus insulin glargine (one injection) and one injection of short-acting insulin regimen. Change in HbA1c and fasting blood glucose (FBG) at 16 weeks, and the proportion of patients achieving HbA1c < 7% at 16 weeks were evaluated. Safety was assessed by occurrence of adverse events, primarily hypoglycaemia. Out of 397 patients enrolled, 375 were analysed and 361 were included in the study population. In the study population, the mean reduction in HbA1c and FBG from baseline to the end point was 1.60% [standard deviation (SD) ± 1.07%] (P < 0.001) and 76.26 (SD ± 57.00) mg/dl] (P < 0.001), respectively, corresponding to a 23% and 34% relative reduction, respectively. The percentage of patients achieving HbA1c level < 7% was significantly higher at 16 weeks than at 4 weeks (42.7% vs. 7.6%). A total of 24 patients (6.04%) reported hypoglycaemia at the 16-week visit. A significant mean reduction in HbA1c and FBG levels (P < 0.001) was observed among the treatment subgroups (insulin glargine alone and insulin glargine + short-acting insulin). In this observational study, initiation of insulin glargine plus OADs in patients with T2DM who failed to achieve glycaemic control on pre-mixed insulin led to significant overall improvements in HbA1c and FBG levels.

Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy.

Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily. Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose. Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone. Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk.