Basal Insulin In Type Research Articles

Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1

AimsThe ONWARDS phase 3a clinical trials evaluated once-weekly insulin icodec (icodec) versus once-daily basal insulin in type 2 diabetes. This analysis investigated the treatment-related experiences of participants from ONWARDS 5 and 2, and physicians from ONWARDS 1. MethodsPatient-reported outcomes were only collected during ONWARDS 5 (icodec with a dosing guide app vs. once-daily basal analogues) and 2 (icodec vs. once-daily insulin degludec). ONWARDS 1 (icodec vs. once-daily insulin glargine U100) physicians’ treatment preferences and satisfaction were obtained via an online survey. ResultsIn ONWARDS 5 and 2, there was a statistically significantly greater increase in total treatment satisfaction from baseline to end of treatment for icodec/icodec with app versus once-daily comparators, mostly driven by participants’ willingness to continue and recommend treatment. In ONWARDS 2, 93.7 % of icodec users preferred once-weekly over once-daily basal insulin, mainly owing to less frequent injections and ease of use. ONWARDS 1 physicians reported greater satisfaction with once-weekly than with once-daily basal insulin and were more likely to recommend once-weekly injections. ConclusionsThese results demonstrate improved treatment satisfaction with, and strong preferences for, once-weekly versus once-daily basal insulin. Treatment convenience and willingness to continue and recommend once-weekly basal insulin treatment were highlighted.Clinical trial registrations: ONWARDS 1: NCT04460885; ONWARDS 2: NCT04770532; ONWARDS 5: NCT04760626

824-P: No Evidence of Increased Physical Activity–Related Hypoglycemia with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in Type 1 Diabetes—ONWARDS 6

824-P: No Evidence of Increased Physical Activity–Related Hypoglycemia with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in Type 1 Diabetes—ONWARDS 6

Cardiovascular and renal outcomes of GLP-1 receptor agonists vs. DPP-4 inhibitors and basal insulin in type 2 diabetes mellitus: A systematic review and meta-analysis.

To compare the cardiovascular and renal outcomes of GLP-1 RA versus DPP4i and basal insulin in the management of T2DM. Data from 22 studies involving over 200,000 participants were pooled using the inverse variance method and random-effects meta-analysis. The review was reported in accordance with PRISMA. Compared with DPP4i, treatment with GLP-1 RA was associated with a greater benefit on composite cardiovascular outcomes (HR:0.77, 95% CI:0.69-0.87), myocardial infarction (HR:0.82, 95% CI:0.69-0.97), stroke (HR:0.83, 95% CI: 0.74-0.93), cardiovascular mortality (HR:0.76, 95% CI:0.68-0.85) and all-cause mortality (HR:0.65, 95% CI:0.48-0.90). There was no difference in effect on heart failure (HR:0.97, 95% CI:0.82-1.15). Compared with basal insulin, GLP-1 RA was associated with better effects on composite cardiovascular outcomes (HR:0.62, 95% CI:0.48-0.79), heart failure (HR:0.57, 95% CI:0.35-0.92), myocardial infarction (HR:0.70, 95% CI:0.58-0.85), stroke (HR:0.50, 95% CI:0.40-0.63) and all-cause mortality (HR:0.31, 95% CI:0.20-0.48). Evidence from a small number of studies suggests that GLP-1 RA had better effects on composite and individual renal outcomes, such as eGFR, compared with either DPP4i and basal insulin. Available evidence suggests that treating T2DM with GLP-1 RA can yield better benefits on composite and specific cardiorenal outcomes than with DPP4i and basal insulin. CRD42022335504.

Insulin Glargine versus Neutral Protamine Hagedorn Insulin in Young and Preschool Children with Type 1 Diabetes Mellitus

Background: Diabetic patients need to maintain tight glycemic control to avoid long term complications. Children need to achieve tight control without the risk of hypoglycemic excursions. Objective: To assess the safety and efficacy of insulin glargine as a basal insulin in type 1 diabetic children aged 3 to 8 years old in comparison to neutral protamine Hagedorn (NPH) insulin as regards the key parameters of diabetes management and low-grade inflammation. Patients and Methods: Fifty children aged 3-8 years old with type 1 diabetes mellitus following in pediatric diabetes clinic, Ain Shams University Hospital were enrolled in this study. They were randomized into two groups, group A: shifted from NPH insulin to basal-bolus regimen using insulin glargine once a day and group B: kept on using NPH insulin two to three times a day. Both used regular insulin or rapid acting analogues at mealtime. Results: At six months, weight gain was significantly higher among group B patients 0.6 kg (±0.14 SD) vs 0.38 kg, mean fasting blood sugar was lower in group A, 109.1(+17) mg/dl versus 125.3(+20) mg/dl in group B. HbA1C showed significant improvement in both groups with tight control, however group A was better with a mean of 6.7(+0.5)% versus 7.4(+0.7) and still with significantly less hypoglycemic excursions. Hs-CRP as a marker of inflammation showed significant drop with better overall control independent of the basal insulin used. Conclusion: Insulin glargine as once daily basal insulin is safe in achieving good glycemic control in young and preschool children with less hypoglycemic excursions.

Association of a SNP in the IAPP gene and hyperglycemia on β-cell dysfunction in type 2 diabetes: the Toon Genome Study.

In type 2 diabetes, the significant pathological change in pancreatic islets is amyloid deposits. Its major component is islet amyloid polypeptide (IAPP). The objective of this study was to evaluate the possibility that the effect of the IAPP genotype on β-cell dysfunction in type 2 diabetes is modified by variations in plasma glucose levels. Participants from the Toon Genome Study underwent a 75g OGTT for the diagnosis of glucose tolerance and the evaluation of insulin secretion. We examined the effect of a SNP, rs77397980, on β-cell function by analyzing an interaction (statistics) between the IAPP genotype and AUC glucose. The ratio of the C-allele carriers was essentially the same among subjects with normal glucose tolerance, impaired glucose tolerance and diabetes. In subjects with diabetes, along with an increase in AUC glucose, fasting insulin remained constant in the T/T homozygotes and appeared to decrease in the C-allele carriers. A homeostasis model assessment (HOMA)-IR appeared to be increased in the former and decreased in the latter. In subjects with diabetes stratified into cases with higher AUC glucose than the median, fasting insulin and HOMA-IR were lower in the C-allele carriers than in the T/T homozygotes. An interaction between the IAPP genotype and AUC glucose was indicated in the effect on HOMA-IR. The possibility that the association between IAPP genotype and basal insulin level is modified by variation in plasma glucose, resulting in a decreased basal insulin in type 2 diabetes, cannot be excluded. The online version contains supplementary material available at 10.1007/s13340-021-00523-4.

Glucagon-like peptide-1 receptor agonist versus basal insulin in type-2 diabetic patients: An efficacy and safety analysis

Purpose: To compare the effectiveness of glucagon-like peptide 1 receptor agonist with that of basal insulin in type 2 diabetes patients.
 Methods: Type-2 diabetes patients who were insensitive to metformin were treated with glucagon-like peptide 1 receptor agonist (GP cohort, n = 115) or basal insulin (BI cohort, n = 152) with metformin. Hemoglobin A1c (HbA1c) level and body weight were determined, and adverse effects also recorded.
 Results: After 16 weeks of treatment, glucagon-like peptide 1 receptor agonist did not significantly reduce HbA1c levels (7.45 ± 2.11 % vs. 7.01 ± 2.01, p = 0.107). In contrast, basal insulin significantly reduced the levels of HbA1c (7.91 ± 2.98 % vs. 7.13 ± 2.22 %, p = 0.010, q = 3.852). Glucagon-likepeptide 1 receptor agonist reduced the body weight of patients (65.25 ± 7.55 kg vs. 62.16 ± 6.15 kg, p = 0.0008, q = 5.121), unlike basal insulin (63.71 ± 6.15 vs. 62.65 ± 6.76 kg, p = 0.154).
 Conclusion: Glucagon-like peptide 1 receptor agonist and basal insulin + metformin produce identical effectiveness in the treatment of type-2 diabetic patients.
 Keywords: Glucagon-like peptide-1 receptor agonist, Glycemic control, Insulin, Metformin, Type-2 diabetes

Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis.

To compare the efficacy and safety of short- and long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin, in patients with type 2 diabetes. Randomized controlled trials comparing the coadministration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications, 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs. Differences in HbA1c, fasting plasma glucose, body weight, and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis. There were relatively small numbers of available publications, some heterogeneity regarding protocols, and differences in the GLP-1 RA compound used. Long-acting GLP-1 RAs more effectively reduced HbA1c (∆ -6 mmol/mol [95% CI -10; -2], P = 0.007), fasting plasma glucose (∆ -0.7 mmol/L [-1.2; -0.3], P = 0.007), and body weight (∆ -1.4 kg [-2.2; -0.6], P = 0.002) and raised the proportion of patients achieving an HbA1c target <7.0% (<53 mmol/mol) (P = 0.03) more than the short-acting ones. Patients reporting symptomatic (P = 0.048) but not severe (P = 0.96) hypoglycemia were fewer with long- versus short-acting GLP-1 RAs added to insulin. A lower proportion of patients reported nausea (-52%, P < 0.0001) or vomiting (-36%, P = 0.0002) with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA1c, fasting plasma glucose, and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastrointestinal tolerability.

Using 2nd generation basal insulins in type 2 diabetes: Costs and savings in a comparative economic analysis in Italy, based on the BRIGHT study

Background and aimsTo evaluate the economic impact of using 2nd generation basal insulin analogs, Glargine 300 Units/ml (Gla-300) vs Degludec 100 Units/ml (IDeg-100), in patients with type 2 diabetes (T2D). Methods and resultsAn economic analysis was conducted using findings from the BRIGHT study (the first controlled, head-to-head study comparing Gla-300 vs IDeg-100), and costs for the Italian National Healthcare Service (NHS). A cost-minimization analysis (CMA) and a budget impact analysis (BIA) were conducted. Only pharmacological costs were included in the analysis. The CMA estimated patient treatment costs at 24 weeks and 1 year; the BIA assessed the economic impact of treating the overall Italian population of T2D insulin-naïve patients, who initiated insulin treatment during the period September 2017–August 2018 (N = 55 318).In the BIA, four different scenarios were compared: i) all patients receive IDeg-100 (Scenario A); ii) 61% of patients receive Gla-300, 39% IDeg-100 (Scenario B); iii) 80% of patients receive Gla-300, 20% IDeg-100 (Scenario C); iv) all patients treated with Gla-300 (Scenario D). The average treatment costs per patient were lower with Gla-300 vs IDeg-100 (at 24 weeks: €129 vs €161; at 1 year: €324 vs €409, respectively). Results of the BIA showed that comparing Scenario D vs Scenario A, total savings would amount to €1.76 million at 24 weeks, €4.73 million at 1 year, €5.53 million at 2 years. ConclusionA larger use of Gla-300 vs IDeg-100 for the treatment of T2D patients would lead to a relevant reduction of therapy costs in Italy.

A review of the NG17 recommendations for the use of basal insulin in type 1 diabetes.

AimsTo revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes).MethodsWe replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta‐analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily.ResultsThe absolute changes in HbA1c were similar to those reported in the NG17. However, all 95% credible intervals for change in HbA1c point estimates crossed the line of null effect, except for detemir twice daily (in the NICE and extended 2017 NMAs) and NPH four times daily. In the detemir twice‐daily centred post hoc analysis, the 95% credible intervals for change in HbA1c crossed the line of null effect for all basal therapies, except NPH.ConclusionsIn NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat‐to‐target, which minimize differences in HbA1c. In the NMAs, statistical significance was severely undermined by the wide credible intervals. Despite these limitations, point estimates of HbA1c were used to rank the insulins and formed the basis of NG17 guidance. This study queries whether such analyses should be used to make specific clinical recommendations.

Fixed versus flexible combination of GLP-1 receptor agonists with basal insulin in type 2 diabetes: A retrospective multicentre comparative effectiveness study.

Background and AimsThe combination of basal insulin (BI) and GLP‐1 receptor agonists (GLP‐1RAs) is a rational and effective therapy for patients with uncontrolled type 2 diabetes (T2D). We compared the effectiveness of fixed and flexible BI/GLP‐1RA combinations using routinely accumulated clinical data.MethodsThis was a retrospective, multicentre, real‐world study concerning T2D patients initiating a fixed or flexible BI/GLP‐1RA combination (NCT03959865). The primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight, fasting plasma glucose (FPG) and systolic blood pressure (SBP). Confounding was addressed by propensity score matching (PSM) or multivariable adjustment (MVA).ResultsA total of 609 patients were included in the study, 131 in the fixed group and 478 in the flexible group. The two groups differed in terms of diabetes duration, body weight and concomitant medications. After 5.7 months, observed HbA1c reductions were 0.6% and 0.8%, and body weight reductions were 2.8 kg and 1.2 kg in the flexible and fixed groups, respectively. Following PSM, HbA1c declined similarly in the two groups, whereas reduction in body weight was significantly in favour of the flexible combination. Findings were robust in sensitivity analyses, with the exception that, with MVA, a significantly higher reduction in HbA1c was detected in the fixed group. Final doses of BI were higher in the fixed group, whereas those of GLP‐1RA were higher in the flexible group.ConclusionsIn routine specialist care, initiation of the fixed or flexible BI/GLP‐1RA combination allowed similar improvement in glycaemic control, but greater weight loss was observed with the flexible combination. This difference reflected dosages of BI and GLP‐1RAs.

Appropriate Titration of Basal Insulin in Type 2 Diabetes and the Potential Role of the Pharmacist.

A substantial proportion of patients with suboptimal control of their type 2 diabetes experience delays in treatment intensification. Additionally, patients often experience overuse of basal insulin, commonly referred to as “over-basalization,” whereby basal insulin continues to be uptitrated in order to meet targets, when addition of a mealtime bolus insulin dose may be a more appropriate option. In order to overcome these challenges, there is a need to develop the capacity of allied healthcare professionals to provide appropriate support to these patients, such as during initiation or titration of basal insulin. Pharmacists play an integral role in healthcare delivery, with patients seeing their pharmacist, on average, seven times more often than their primary care physician. This places pharmacists in a unique position to provide diabetes education and care, which may help patients avoid clinical inertia. Nevertheless, the management of the disease with basal insulin is becoming increasingly complex, with growing numbers of treatment options (such as recent second-generation longer-acting basal insulin formulations) and frequently updated titration algorithms. The two most common titration schedules specify either increasing doses by a set amount every 2–3 days or a treat-to-target strategy. Neither schedule has been shown to be superior, and the decision to use one or the other should be based on a discussion between the clinician and patient after assessment of mental and physical acumen, comfort of both parties, and follow-up plans. This review article discusses basal insulin therapy options and titration algorithms from the unique perspective of the pharmacist in order to help ensure that optimal antidiabetes therapy is initiated, appropriately titrated, and maintained.Funding: Sanofi US, Inc.

When should bolus insulin be added to basal insulin in type 2 diabetes?

Ericson, Kevin MD; Witt, Anthony MD; Morningstar, Alexa DO; Isch, Jason PharmD Author Information

Impact of Insulin Degludec in Type 2 Diabetes: Real-World Data on Effectiveness and Safety.

IntroductionReal-world evidence on effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. The aim of the study was to evaluate patterns of use and the long-term effectiveness and safety of IDeg in routine clinical practice.MethodsThis was an observational longitudinal study. A retrospective chart review of all patients with type 2 diabetes treated with IDeg was performed and temporal trends in clinical outcomes were assessed. All data was stratified by treatment modality: the switch group consisted of patients already treated with another basal insulin before initiating IDeg; the add-on group consisted of basal insulin-naïve patients.ResultsOverall, 247 patients were analyzed (55 in the add-on group and 192 in the switch group), mean age 67.0 ± 10.9 years ,and diabetes duration 16.3 ± 8.9 years. Median (interquartile range) follow-up was 9.7 (8.0–11.9) months. In the add-on group, improvements were found in glycated hemoglobin (HbA1c) (– 1.68%; p < 0.0001), fasting blood glucose (FBG) (– 64.7 mg/dL; p < 0.0001), post-prandial glucose (PPG) (– 81.1 mg/dl; p < 0.0001), and glycemic variability (i.e., standard deviation of blood glucose) (– 11.6 mg/dl; p = 0.04). Even in the switch group, improvements were found in HbA1c (– 0.57%; p < 0.0001), FBG (– 28.1 mg/dL; p < 0.0001), and PPG (– 22.6 mg/dl; p = 0.001). Body weight increase during the follow-up was not statistically significant vs. baseline in both groups. Benefits on overall, nocturnal, and severe hypoglycemia were found in the switch group.ConclusionThese real-world data documented that initiating IDeg or switching to IDeg from other basal insulins in type 2 diabetes was associated with significant improvement in metabolic control without significant weight gain; a decrease in the risk of hypoglycemia was observed when switching to IDeg from another basal insulin.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0511-4) contains supplementary material, which is available to authorized users.

Safety and Efficacy of DPP4 Inhibitor and Basal Insulin in Type 2 Diabetes: An Updated Review and Challenging Clinical Scenarios.

The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin secretion and inhibit glucagon production. As monotherapy, they reduce the hemoglobin A1c level by about 0.6–0.8%. The addition of a DPP4 inhibitor to basal insulin is an attractive option, because they lower both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain. The present review summarizes the extensive evidence on the combination therapy of DPP4 inhibitors and insulin-based regimens in patients with type 2 diabetes. We focus our discussion on challenging clinical scenarios including patients with chronic renal impairment, elderly persons and hospitalized patients. The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia. In addition, several randomized-controlled trials have shown that the use of DPP4 inhibitors in combination with basal insulin represents an alternative to the basal-bolus insulin regimen in hospitalized patients with type 2 diabetes.

A practical approach and algorithm for intensifying beyond basal insulin in type 2 diabetes

Despite the availability of long-term data demonstrating the benefits of timely and aggressive intensification of antihyperglycaemic regimens among individuals with type 2 diabetes, intensification beyond basal insulin continues to be suboptimal and a global challenge. This review summarizes the evidence surrounding the various options of advancing glucose-lowering management beyond basal insulin and provides a practical algorithm to assist in optimizing patient care and enhancing glycaemic target achievements.

PDB17 - A Real-World Data Analysis Evaluating the Time to Glycemic Control After Initiation of Basal Insulin in Type 2 Diabetic Patients

PDB17 - A Real-World Data Analysis Evaluating the Time to Glycemic Control After Initiation of Basal Insulin in Type 2 Diabetic Patients

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes.

BackgroundWe assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden.MethodsThe Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions.ResultsFrom the ITC, decreases in HbA1c were –1.32% and –0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were –1.29 and –0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model.ConclusionsThe costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal insulin) were below the threshold considered low by Swedish authorities. In some scenarios, liraglutide and IDegLira were cost-saving.

Nutritional Insulin or Glp-1 Receptor Agonist: Crossroads in the Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a progressive disease due to worsening of pancreatic beta cell function over time ( 1. Fonseca V.A. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009; 32: S151-S156 Crossref PubMed Google Scholar ). Patients with classical T2DM initially respond to noninsulin antidiabetic agents, but insulin therapy becomes essential at some point. Most patients treated with sulfonylurea drugs and metformin need insulin after about 9 years of therapy ( 2. Turner R.C. Cull C.A. Frighi V. Holman R.R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999; 281: 2005-2012 Crossref PubMed Scopus (2167) Google Scholar ). Once required, insulin is often prescribed as a single daily injection of basal insulin. However, over time, more frequent injections are needed to control postprandial hyperglycemia and achieve a target level of glycated hemoglobin (HbA1c). While insulin is the most effective treatment for hyperglycemia, insulin use is associated with weight gain and increased risk of hypoglycemia ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar ). Moreover, multiple daily insulin injections are prone to errors and may be burdensome for many older patients with T2DM. Therefore, alternatives to daily insulin injections are welcomed by patients as well as their physicians. Adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to a treatment regimen that includes basal insulin and oral antidiabetic agents is an attractive option. Compared to the basal-bolus insulin regimen, it requires a smaller number of injections and is associated with lower risks of weight gain and hypoglycemia ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar ). A GLP-1RA may be added to the basal insulin therapy or vice versa. Randomized clinical trials have shown equivalent glycemic control with basal insulin plus a GLP-1RA and basal insulin plus nutritional insulin ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar , 4. Mathieu C. Rodbard H.W. Cariou B. et al. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON). Diabetes Obes Metab. 2014; 16: 636-644 Crossref PubMed Scopus (144) Google Scholar ). However, there are concerns about using GLP-1RA with insulin due to increased treatment cost.

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients’ exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.

Options for intensification of basal insulin in type 2 diabetes: Premeal insulin or short-acting GLP-1 receptor agonists?

Type 2 diabetes is an evolutive disease with a progressive defect of beta-cell insulin secretion. This characteristic points to a need for treatment that takes into account such a natural history. When oral antidiabetic drugs fail to achieve the patient's target HbA1c level, basal insulin treatment is usually initiated and titrated in association with oral drugs to manage fasting hyperglycaemia. Over a period of time, it is enough to simply achieve the HbA1c target. However, when even a good fasting blood glucose level is no longer sufficient to control overall glycaemia, then prandial treatment must be combined with the titrated basal insulin to deal with the postprandial hyperglycaemia responsible for the elevation of HbA1c.Of the different therapeutic options now available for this, rapid-acting insulins and GLP-1 receptor agonists (RAs) can be used. Rapid-acting insulins can be added either at each meal, achieving full insulin supplementation with a basal-bolus regimen, or at the main meal only as a “basal-plus” regimen. Compared with the full basal-bolus, the basal-plus strategy is associated with fewer injections, yet provides similar efficacy in terms of HbA1c improvement, but with less weight gain and lower hypoglycaemic risk. As for GLP-1 RAs, numerous studies, and especially those using short-acting GLP-1 RAs, have demonstrated more pronounced effects on postprandial hyperglycaemia, good complementary effects with basal insulin, and significant improvement of HbA1c with no weight gain and a low risk of hypoglycaemia. Similarly, direct and indirect comparisons of the use of rapid-acting insulins and GLP-1 RAs to intensify basal insulin have shown comparable efficacy in terms of HbA1c control, but with less weight gain and fewer hypoglycaemic episodes with GLP-1 RAs.