Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study)

Bajaj, Harpreet S.; Venn, Karri; Ye, Chenglin; Patrick, Avril; Kalra, Sarathi; Khandwala, Hasnain; Aslam, Nadeem; Twum-Barima, David; Aronson, Ronnie

doi:10.2337/dc16-1582

Cited by 56 publications

(43 citation statements)

References 36 publications

(27 reference statements)

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“…[23][24][25] Bajaj et al demonstrated reduced glucose variability with basal insulin and GLP-1 RA therapy compared to other insulin-based regimens. 26 In 160 T2D patients with HbA1c £7.5%, using blinded CGM for 6 days, this study showed that basal insulin with GLP-1 RA therapy reduced the standard deviation of daily glucose compared to basal insulin with oral medications, basal/bolus regimen, and premixed insulin regimens (P = 0.03, P = <0.01, and P = 0.01, respectively). This observation persisted even when adjusted for HbA1c.…”

Section: Glucose Variabilitymentioning

confidence: 73%

Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes

Carlson¹,

Mullen²,

Bergenstal³

2017

Diabetes Technology & Therapeutics

139

100

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Background: Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions.CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions.The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management.

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Section: Glucose Variabilitymentioning

confidence: 73%

Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes

Carlson¹,

Mullen²,

Bergenstal³

2017

Diabetes Technology & Therapeutics

139

100

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“…HbA 1c reduction and weight loss are largely accomplished within 15 weeks and can be expected to have reached maximal [63][64][65][66] If the HbA 1c is <8%, or if the patient is at high risk for hypoglycemia for any reason (e.g., hypoglycemia unawareness, or history of severe or frequent hypoglycemia), it is advisable to reduce the dosage of insulin and/or other antihyperglycemic agents by a moderate amount to reduce the risk of hypoglycemia when adding another highly effective agent.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

Rodbard¹

2018

Diabetes Technology & Therapeutics

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GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA 1c and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time. They have very low risk of hypoglycemia unless used in conjunction with insulin or insulin secretagogues. Two coformulations of GLP-1 RAs together with long-acting basal insulin are available for daily use. The original GLP-1 RA, exenatide, requires twice-daily injections; two short-acting analogs are given once daily. Three currently available long-acting GLP-1 RAs are injected once weekly, providing greater convenience and potentially improving patient adherence. Semaglutide appears to be the most effective in terms of HbA 1c reduction and weight loss. GLP-1 RAs can be combined with all classes of antihyperglycemic agents except DPP-4 inhibitors. Current studies are exploring the use of an implantable osmotic pump for long-term administration of a rapid acting analog (exenatide), an oral preparation of semaglutide, benefits for management of obesity and nonalcoholic steatohepatitis, and mechanisms of cardioprotective effects.

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“…Pooled data from three trials of Lixi as add‐on therapy to BI showed a significant reduction in GV (measured as SD of SMPG, MAG, MAGE, HBGI, LBGI and AUC for fasting glucose) with Lixi, accompanied by no increase in hypoglycaemia risk . A recent report investigating GV in four different therapy cohorts found that, in controlled T2D, the lowest GV and hypoglycaemia frequency were achieved with a regimen of BI plus the GLP‐1RA liraglutide (Lira) . Similarly, modest improvements in only one measure of GV (coefficient of variation) were seen at 26 weeks in a study of basal‐bolus insulin vs BI plus the GLP‐1RA exenatide .…”

Section: Discussionmentioning

confidence: 99%

“…Glycated haemoglobin (HbA1c) is commonly used to estimate mean glucose exposure over 2 to 3 months to assess glycaemic control in patients with diabetes; however, HbA1c does not reflect daily excursions in blood glucose or glycaemic variability (GV) . Patients with type 2 diabetes (T2D), despite achieving within‐target control of HbA1c, may still show substantial GV . Increased GV correlates with increased hypoglycaemia, may adversely affect endothelial function and oxidative stress, and probably contributes to cardiovascular complications in diabetes …”

Section: Introductionmentioning

confidence: 99%

“…Because they are known to reduce postprandial glucose (PPG) excursions, GLP‐1RAs may have a unique benefit in the reduction of GV. Two recent studies of regimens that included GLP‐1RAs reported significant reductions (improvements) in GV for such regimens compared with insulin alone and other injectable combination therapies . iGlarLixi, a combination of the GLP‐1RA lixisenatide (Lixi) and long‐acting basal insulin (BI) glargine 100 units/mL (iGlar), is delivered through a single daily injection for T2D treatment.…”

Section: Introductionmentioning

confidence: 99%

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Insulin glargine/lixisenatide fixed‐ratio combination improves glycaemic variability and control without increasing hypoglycaemia

Aronson

Umpiérrez

Stager

et al. 2018

Diabetes Obesity Metabolism

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Maintaining optimal glycaemic control reduces the risk of micro‐ and macrovascular complications in patients with type 2 diabetes. Typically, glycaemic control is based on glycated haemoglobin (HbA1c) as a measure of mean glucose concentration; however, this marker does not accurately reflect glycaemic variability (GV), which is characterized by the amplitude, frequency and duration of hypo‐ and hyperglycaemic fluctuations. In the present study, we analysed data from the LixiLan‐O trial, which compared iGlarLixi, a titratable fixed‐ratio combination of the glucagon‐like peptide‐1 receptor agonist lixisenatide (Lixi) and long‐acting basal insulin glargine 100 units/mL (iGlar), with its individual components, and the LixiLan‐L trial, which compared iGlarLixi with iGlar. The GV features that were measured were mean and SD of self‐measured plasma glucose (SMPG), high blood glucose index (HBGI) and low blood glucose index, area under the SMPG curve for each patient (AUCn), mean absolute glucose (MAG) and mean amplitude of glycaemic excursions (MAGE). By week 30, iGlarLixi improved all GV markers from baseline, with no increased hypoglycaemia risk. Significant improvements were observed in SMPG, SD of SMPG, HBGI, AUCn, MAG and MAGE compared with iGlar, and in SMPG, HBGI and AUCn, compared with Lixi.

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Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study)

Cited by 56 publications

References 36 publications

Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes

Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

Insulin glargine/lixisenatide fixed‐ratio combination improves glycaemic variability and control without increasing hypoglycaemia

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