Basal Insulin In Patients Research Articles

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving Basal Insulin.

IntroductionOnce-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin.MethodsA systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework.ResultsIn total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c (− 0.88% to − 1.39% vs comparators) and weight (− 1.49 to − 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators.ConclusionOnce-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs.FundingNovo Nordisk.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0428-y) contains supplementary material, which is available to authorized users.

Probability of Achieving Glycemic Control with Basal Insulin in Patients with Type 2 Diabetes in Real-World Practice in the USA.

IntroductionBasal insulin (BI) plays an important role in treating type 2 diabetes (T2D), especially when oral antidiabetic (OAD) medications are insufficient for glycemic control. We conducted a retrospective, observational study using electronic medical records (EMR) data from the IBM® Explorys database to evaluate the probability of achieving glycemic control over 24 months after BI initiation in patients with T2D in the USA.MethodsA cohort of 6597 patients with T2D who started BI following OAD(s) and had at least one valid glycated hemoglobin (HbA1c) result recorded both within 90 days before and 720 days after BI initiation were selected. We estimated the changes from baseline in HbA1c every 6 months, the quarterly conditional probabilities of reaching HbA1c < 7% if a patient had not achieved glycemic control prior to each quarter (Q), and the cumulative probability of reaching glycemic control over 24 months.ResultsOur cohort was representative of patients with T2D who initiated BI from OADs in the USA. The average HbA1c was 9.1% at BI initiation, and decreased robustly (1.5%) in the first 6 months after initiation with no further reductions thereafter. The conditional probability of reaching glycemic control decreased rapidly in the first year (26.6% in Q2; 17.6% in Q3; 8.6% in Q4), and then remained low (≤ 6.1%) for each quarter in the second year. Cumulatively, about 38% of patients reached HbA1c < 7% in the first year; only approximately 8% more did so in the second year.ConclusionOur study of real-world data from a large US EMR database suggested that among patients with T2D who initiated BI after OADs, the likelihood of reaching glycemic control diminished over time, and remained low from 12 months onwards. Additional treatment options should be considered if patients do not reach glycemic control within 12 months of BI initiation.FundingSanofi Corporation.

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.

A real-world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672).

SummaryAimThis is a pre‐post observational study from an endocrinology ambulatory care practice which assessed the effectiveness and safety following the addition of a glucagon‐like peptide‐1 (GLP‐1) agonist, weekly exenatide (Bydureon), to basal insulin therapy in patients with type 2 diabetes mellitus (T2DM). Liraglutide plus basal insulin served as a comparison group.Materials and methodsA data collection form was utilized to collect study‐related information. The primary study outcome was change in HbA1c from baseline to 12 months after GLP‐1 receptor agonist therapy was added to basal insulin therapy. Secondary outcomes were change in weight, percentage of patients achieving an HbA1c of <7% (53 mmol/mol) or ≤6.5% (48 mmol/mol) and changes in blood pressure and lipid parameters. Safety was assessed by a collection of reported adverse events.ResultsOne‐hundred and fifty patients met inclusion criteria (seventy‐five per treatment arm). After 1 year of therapy, HbA1c decreased by 0.7% in the entire cohort (once‐weekly exenatide: −0.7%; once‐daily liraglutide: −0.8%; no significant between‐group difference). More subjects in the weekly exenatide arm achieved an HbA1c < 7% (53 mmol/mol) (P = .03), but a comparable number achieved an HbA1c ≤ 6.5% (48 mmol/mol). Although significantly more patients achieved an HbA1c < 7% (53 mmol/mol) in the once‐weekly exenatide arm, the baseline HbA1c was lower (7.9%) than the liraglutide arm (8.4%). No significant differences were observed between groups for other secondary outcomes. A similar number of subjects discontinued therapy, mainly due to gastrointestinal‐ill effects, and hypoglycaemia incidence did not increase compared with the previous year.ConclusionThe addition of once‐weekly exenatide to basal insulin was associated with appreciable reductions in HbA1c and weight without an increase in hypoglycaemia.

Diabetes injectable therapy: type 2 diabetes management in Danish practice

Most diabetes care is done by GPs in Denmark. This study aimed to identify the barriers for GPs in initiating injectable therapies and reasons for referral to specialists. The web interview conducted included 85 GPs and 30 specialists experienced in type 2 diabetes (T2D). GPs felt more comfortable with initiating the first injectable therapy (defined as a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or basal insulin) than the second (defined as adding a basal insulin in patients treated with a GLP-1 RA (± oral anti-diabetic treatments [OADs]), or adding either a GLP-1 RA or a bolus insulin in patients treated with basal insulin (± OADs). The main barriers to initiating injectables were related to the complexity of available injectable therapies and the lack of comfort with complex patient profiles, namely patients with difficult glycemia control or significant comorbidities, whom GPs would rather refer to specialists. Main attributes that would increase the GPs’ comfort level with initiation of injectables are low risk of hypoglycemia, glycemic control improvement and ease of use of the treatment. An injectable therapy with such attributes could help to overcome barriers to initiating injectable in primary care.

Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization.

IntroductionHypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D.MethodsHypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined.ResultsOf 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs.ConclusionsUS patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden.FundingSanofi US, Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0592-x) contains supplementary material, which is available to authorized users.

Satisfaction of switching to combination therapy with lixisenatide and basal insulin in patients with type 2 diabetes receiving multiple daily insulin injection therapy: A randomized controlled trial.

Aims/IntroductionWe compared the satisfaction levels of patients with type 2 diabetes undergoing combination therapy with lixisenatide (LIX) and basal insulin with that of patients undergoing multiple daily insulin injection (MDI) therapy.Materials and MethodsThe study was a 12‐week open‐label, randomized, multicenter, controlled trial. Participants were Japanese patients with type 2 diabetes receiving MDI for >3 months. Patients were randomly assigned to each treatment cohort: (i) a group that continued MDI (MDI group); and (ii) a group that switched from MDI to combination therapy with LIX and basal insulin (LIX group). The primary outcome was change in Diabetes Treatment Satisfaction Questionnaire scores from baseline to 12 weeks between these two groups. Key secondary outcomes were glycated hemoglobin and body weight changes.ResultsA total of 31 patients were initially enrolled in the study, and 26 of them completed the study. The change in Diabetes Treatment Satisfaction Questionnaire scores in the LIX group was significantly greater compared with that in the MDI group. Mean changes in glycated hemoglobin levels were −0.05 ± 0.37% in the MDI group and 0.04 ± 0.38% in the LIX group (P = 0.36). Mean changes in body weight were +0.6 ± 1.8 kg in the MDI group and −2.5 ± 1.8 kg in the LIX group (P < 0.01).ConclusionsSwitching from MDI to combination therapy with LIX and basal insulin improved satisfaction levels while maintaining glycemic control in Japanese patients with type 2 diabetes.

Once weekly glucagon-like peptide-1 receptor agonist albiglutide vs. prandial insulin added to basal insulin in patients with type 2 diabetes mellitus: Results over 52 weeks

We have previously reported that once-weekly albiglutide was noninferior to thrice-daily lispro for glycemic lowering, with decreased weight and risk of hypoglycemia, in patients inadequately controlled on basal insulin over 26 weeks. Findings after 52 weeks reveal similar responses to albiglutide as an add-on to insulin glargine.

Short Term Efficacy and Safety of Insulin Glargine in Type 2 Diabetes Inadequately Controlled with Single or Two Oral Agents: A Prospective, Open Label Study.

Basal insulin is among the second line treatment options for Type 2 Diabetes Mellitus (T2DM). Efficacy and safety of basal insulin in patients of T2DM, uncontrolled with Oral Antidiabetic Agents (OAAs) remains understudied in the Indian setting. To assess the efficacy and safety of insulin glargine in patients with T2DM who have uncontrolled glycaemic levels despite single or two OAAs therapy. In this prospective, open label study, T2DM patients above 40 years of age, having inadequate glycaemic control [Glycosylated Haemoglobin (HbA1c) above 8% and/or fasting glucose level of 140 mg/dl and above] with single or two OAAs over three consecutive months were included. Dosing of insulin glargine was adjusted as per Fasting Blood Glucose (FBG) and Post Prandial Blood Glucose (PPBG) levels. Patients were followed for 12 weeks and data was analysed by comparing 12th week findings to baseline values. In 40 cases included in final analysis, mean age was 56.35 ± 6.77 years, 52.5% were females and mean body mass index was 26.96 ± 4.59 kg/m2. Compared to baseline, significant reduction in HbA1c, FBG and PPBG blood glucose (all p<0.05) was seen. HbA1c goal of < 7% was achieved in 37.5% cases. Systolic (p>0.05) and diastolic (p<0.05) blood pressures reduced at 12 weeks as compared to baseline. Increase in weight was modest with mean increase of 1.06 kg (p>0.05). Overall, 14 symptomatic hypoglycaemia events were observed with none being severe. Short term administration of insulin glargine is effective in reducing glycaemia and is safe with lower rates of severe hypoglycaemia. It can be considered in patients with uncontrolled T2DM on mono- or two- OAAs treatment.

Comparative effectiveness and safety of three different basal insulins in patients with type 2 diabetes in a real world setting (ORBIT): a multicentre, prospective, registry study

BackgroundThe three most commonly used basal insulins in patients with type 2 diabetes are neutral protamine Hagedorn (NPH) insulin and the long-acting insulin analogues glargine and detemir. Although randomised controlled trials have shown equivalent efficacy of these three insulins, inconsistencies in safety exist. We aimed to assess the safety and efficacy of these three basal insulins in real-world clinical setting in the ORBIT (Observational Registry for Basal Insulin Treatment) study. MethodsIn this multicentre, 6 month, prospective, registry study, patients were recruited between Nov 25, 2011, and Sept 1, 2014, who were aged 18–80 years, with type 2 diabetes that was inadequately controlled (HbA1C ≥7%, 53 mmol/mol) with oral antidiabetic drugs and who were willing to start treatment with basal insulin were enrolled from 209 hospitals in eight regions of China. Patients who were prescribed any type of insulin in the past 2 years, with clinically significant acute major organ or systemic disease or other condition judged by the investigator that would create difficulty for the 6 month follow-up, or current or planned pregnancy or lactating women were excluded. Type and dose of basal insulin were at the physician's discretion and at the patients' willingness. Assessments were done at baseline (0 month—visit 1), mid-term (3 months—visit 2), and at the end of the study (6 months—visit 3) by investigators during routine practice. During analysis, patients were separated into NPH, glargine, and detemir insulin groups according to their initial prescription of basal insulin. Outcomes included the change in concentration of HbA1c, hypoglycaemia rate, and bodyweight change in the three groups from baseline to 6 months. Propensity scores with regression adjustment were used to balance the baseline differences among the three groups. Intention-to-treat analysis was used to assess the outcomes. FindingsOur findings show that treatment with long-acting insulin analogues is associated with better glycaemic control and less hypoglycaemia and weight gain than treatment with NPH insulin in patients with type 2 diabetes. Interpretation16 341 patients were analysed in the intention-to-treat group and 9002 were analysed in the per-protocol group. In the intention-to-treat population, there were 11 290 (69%) patients treated with glargine, 2135 (13%) patients treated with detemir, and 18% (2916) patients treated with NPH insulin. After controlling for the baseline and process variables in the propensity score regression, the intention-to-treat analysis showed that the reductions in HbA1c in the glargine (2%, SD 2·1, p=0·0014) and detemir (2%, 2·1, p=0·0065) groups were higher than that in the NPH group (2%, 2·2). The detemir group had lower weight gain (−0·1 kg, SD 2·9) than the glargine group (0·1 kg, 3·0; p=0·032) and the NPH group (0·3 kg, 3·1; p<0·0001). Patients in the glargine group had the lowest rate and frequency of minor hypoglycaemia when compared with those in the determir group (10% and 27%, respectively, both p<0·0001) and NPH group (13% and 27%, respectively, both p<0·0001). Whereas no difference was noted in severe hypoglycaemia among the three groups. The rates of severe hypoglycaemia were 0·5% in the glargine group, 0·7% in the determir group, and 0·5% in the NPH groupy (p=0·32 in total), and the frequency of severe hypoglycaemia in the three groups were 6·2, 4·9, and 5·5 times per person per year, respectively (p=0·20 in total). FunderSanofi (Shanghai, China).

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment.

BackgroundThere were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin.MethodsIn this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT.ResultsAmong 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group.ConclusionLong-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Clinical and Economic Outcomes Associated With the Timing of Initiation of Basal Insulin in Patients With Type 2 Diabetes Mellitus Previously Treated With Oral Antidiabetes Drugs

PurposeIn patients with type 2 diabetes mellitus (T2DM) not achieving glycemic targets using oral antidiabetes drugs (OADs), studies suggest that timely insulin initiation has clinical benefits. Insulin initiation at the early versus late stage of disease progression has not been explored in detail. This retrospective database analysis investigated clinical and economic outcomes associated with the timing of insulin initiation in patients with T2DM treated with ≥1 OAD in a real-world US setting. MethodsThis study linked data from the Truven Health MarketScan® Commercial database, Medicare Supplemental database, and Quintiles Electronic Medical Records database. A total of 1830 patients with T2DM were included. Patients were grouped according to their OAD use before basal insulin initiation (1, 2, or ≥3 OADs) as a proxy for the timing of insulin initiation. Clinical and economic outcomes were evaluated over 1 year of follow-up. FindingsDuring follow-up the 1 OAD group, compared with the 2 and ≥3 OADs groups, had a greater reduction in glycosylated hemoglobin A1c (−1.7% vs −1.0% vs −0.9%, respectively; P < 0.0001), greater achievement of glycemic target (38.2% vs 26.7% vs 19.6%, respectively; P < 0.0001), and a lower incidence of hypoglycemia (2.7% vs 6.6% vs 5.0%, respectively; P = 0.0002), with no difference in total health care costs ($21,167 vs $21,060 vs $20,133, respectively). ImplicationsThis study shows that early insulin initiation (represented by the 1 OAD group) may be clinically beneficial to patients with T2DM not controlled with OADs, without adding to costs. This supports the call for timely initiation of individualized insulin therapy in this population.

Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin.

Type 2 diabetes mellitus (T2DM) management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2) inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates a 78-week, randomized, double-blind, placebo-controlled trial investigating the impact of empagliflozin, an SGLT2 inhibitor, as add-on to basal insulin in patients with inadequate glycemic control on basal insulin, with or without metformin and/or a sulfonylurea. Empagliflozin added on to basal insulin resulted in significant and sustained reductions in glycated hemoglobin (HbA1c) levels compared with placebo. Empagliflozin has previously been shown to induce weight loss, and was associated with sustained weight loss in this study. This combination therapy was well tolerated, with similar levels of hypoglycemic adverse events in the empagliflozin and placebo groups over the 78-week treatment period. Urinary tract infections and genital infections, side effects associated with SGLT2 inhibitors, were reported more commonly in the empagliflozin group; however, such events led to treatment discontinuation in very few patients. These findings suggest that, with their complementary mechanisms of action, empagliflozin added on to basal insulin may be a useful treatment option in patients on basal insulin who need additional glycemic control without weight gain.

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway

Background:Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia.Objective:To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway.Methods:The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal–bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed.Results:Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c.Conclusions:Lixisenatide may be considered an economically efficient therapy in combination with basal insulin in the Norwegian setting, due to cost savings, weight loss and associated gains in health-related quality of life.

What happens when patients require intensification from basal insulin? A retrospective audit of clinical practice for the treatment of type 2 diabetes from four Australian centres

AimsLittle is known about clinical practices beyond the initiation of basal insulin in patients with type 2 diabetes mellitus (T2DM) in Australia. To determine the proportion of patients who progressed from basal insulin to each of three possible therapy groups: Group 1 addition of rapid-acting insulin, Group 2 switch to pre-mixed insulin, Group 3 addition of another therapy (incretin, glitazone, sulphonylurea, metformin, acarbose). MethodsRetrospective audit across four Australian hospital clinics. Patients had a diagnosis of T2DM, basal insulin had been initiated and a subsequent treatment intensification/change had occurred during the analysis period (September 2007–March 2012). ResultsPatients were classified into one of three intensification groups for analysis: Group 1, 56.1% (111/198); Group 2, 22.7% (45/198) and Group 3, 21.2% (42/198). Prior to basal insulin initiation, mean T2DM duration was 11 years. Between starting basal insulin and treatment intensification, 42/183 (22.9%) patients achieved the HbA1c target of <7.0% (53mmol/mol).Initiation of basal insulin provided temporary improvement in glycaemic control followed by subsequent deterioration. With further treatment intensification, only 40/180 (22.2%) patients achieved the HbA1c target of <7.0% (53mmol/mol). Patients in the insulin groups gained weight (Group 1, rapid acting insulin, 1.9±7.4kg; Group 2, premixed insulin 2.3±4.8kg); those in Group 3 lost weight (−0.9±13.54kg). Hypoglycaemic episodes were uncommon irrespective of group. ConclusionsThere is continued need for improved patient management; individualised strategies should focus on when to initiate insulin, how to adjust and optimise doses over time and, when required, the introduction of intensification regimens.

A novel rapid - acting oral inhalation human insulin for diabetes mellitus: Afrezza

Afrezza is rapid-acting oral inhalation insulin that is administered at the beginning of each meal. The U.S Food and Drug Administration has approved Afrezza (insulin human) inhalation powder, a rapid-acting inhaled insulin to improve glycemic control in adults ≥18 years of age with Type 1 or Type 2 diabetes mellitus (T1DM or T2DM). Afrezza must be used in combination with long-acting insulin in patients with T1DM. Afrezza may be used with either oral anti-diabetic drugs or basal insulin in patients with T2DM. Afrezza should be administered via oral inhalation using Afrezza inhaler. Dosage adjustment is needed when switching from injection insulin to oral inhalation Afrezza. It is contraindicated in individuals with chronic lung disease and smokers because of the risk of the acute bronchospasm. Before initiating, Afrezza, a complete medical history, physical examination and spirometry (forced expiratory volume 1 sec) results is required in all individuals to identify the potential lung disease. Common adverse reactions in individuals treated with Afrezza include hypoglycemia, cough, throat pain or irritation, headache, and diarrhea.

Lixisenatide Reduces Glycemic Variability When Added to Basal Insulin in Patients with Type 2 Diabetes Mellitus

This analysis evaluated the impact on glycemic variability (GV) of lixisenatide (LIXI) vs. placebo (PBO) as add-on to basal insulin ± oral anti-diabetes drugs (OADs) in patients with type 2 diabetes mellitus (T2DM).

The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus

Introduction: Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal insulin in patients inadequately controlled on these medications and who are undergoing diet and lifestyle modification. GLP-1RAs glucose-dependently increase insulin secretion, decrease glucagon secretion, and slow gastric emptying, thereby improving glycemic control. GLP-1RAs are associated with body weight benefits and low rates of hypoglycemia which are welcome in patients with T2DM.Areas covered: The authors describe the identification of GLP-1RAs as suitable targets for modification with structure-inducing probe technology to improve stability and resistance to proteolytic degradation. Clinical studies have assessed lixisenatide across > 5000 patients as a monotherapy or add-on to a variety of commonly used antidiabetic medications. These studies highlighted the effects of lixisenatide on gastric emptying, explaining its particular improvements in postprandial plasma glucose (PPG) excursions and underscoring its efficacy in combination with insulin glargine. Lixisenatide was well tolerated, with nausea and vomiting being the most frequently reported adverse events.Expert opinion: The once-daily administration of lixisenatide as well as its substantial sustained effect on gastric emptying and, hence, PPG excursions are all important features compared with the other GLP-1RAs. The combination of two injectables, such as basal insulin to lower fasting plasma glucose and a GLP-1RA that curtails PPG excursions, is clinically valuable and could differentiate lixisenatide from other GLP-1RAs, especially from those continuously acting GLP-1RAs with little effect on gastric emptying and PPG excursions.

Comparison of continuous subcutaneous insulin infusion and insulin glargine-based multiple daily insulin aspart injections with preferential adjustment of basal insulin in patients with type 2 diabetes.

The purpose of this study was to evaluate and compare multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine with continuous subcutaneous insulin infusion (CSII) with aspart in patients with type 2 diabetes mellitus (T2DM). It was assessed whether MDI was capable of controlling glycemic index with a higher efficacy than CSII by preferential adjustment of basal insulin with a lower total daily insulin dosage in T2DM. Two hundred patients with T2DM were enrolled in the study and randomly assigned to CSII (n=100) and MDI (n=100; aspart immediately prior to each meal and glargine at bedtime) groups for 12 weeks of therapy. During the last week of each treatment period, the subjects wore a continuous glucose monitoring system for 2–3 days. The dosage of basal insulin was preferentially adjusted to control prior-meal blood glucose levels, and the characteristics of insulin dosage were analyzed. No statistically significant differences were observed between the two groups in hemoglobin A1c (HbA1c), which dropped from 10–11% prior to therapy to 7–7.5% after 12 weeks. After 12 weeks, good glycemic level control was achieved in all patients in the MDI and CSII groups. A statistically significant difference in the dose of insulin between the CSII and MDI groups was observed (P<0.001). In conclusion, no significant differences were found between the two therapies in the incidence of hypoglycemia and HbA1c for the 12 weeks. The basal insulin dosage was significantly decreased in the MDI group compared with that in the CSII group, but the CSII group was superior to MDI group in decreasing fasting blood glucose and shortening the time required for hypoglycemia to meet the targeted level.

A comparison of biphasic insulin aspart and insulin glargine administered with oral antidiabetic drugs in type 2 diabetes mellitus - a systematic review and meta-analysis

It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar). The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI). Five trials, including a total number of 1758 patients followed up from 24 to 28weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3RCTs; WMD (95% CI): -14.70mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR=1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI)=0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI)=1.78kg (1.04; 2.52)]. BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.