Determinants of glycaemic control in a practice setting: the role of weight loss and treatment adherence (The
            <scp>DELTA</scp>
            Study)

Aims To identify change in glycated haemoglobin (HbA1c) for 1 year after treatment intensification in patients with HbA1c >53 mmol/mol (7.0%) while on two classes of oral antidiabetic drugs (OADs). Material and methods A retrospective cohort study was conducted using a regional health plan claims database for the period January 1, 2010 to March 31, 2017. Patients with type 2 diabetes (T2DM) whose treatment was intensified with insulin, a glucagon‐like peptide‐1 receptor agonist or a third OAD within 365 days of having HbA1c ≥53 mmol/mol (7.0%) on two OADs were included. The HbA1c trajectory for 1 year after intensification was estimated using a mixed‐effects regression model. Results The analysis included 1226 patients with a mean ± SD HbA1c at treatment intensification of 74.2 ± 18.7 mmol/mol (8.93 ± 1.7%). HbA1c was higher in the insulin group (74.2 mmol/mol) than in the non‐insulin group (70.6 mmol/mol), as was the HbA1c decrease ( P < 0.01) over the 1‐year follow‐up, particularly in patients with baseline HbA1c >9%. After intensification, insulin‐ and non‐insulin‐treated patients achieved an average change by month in HbA1c of −4.7 mmol/mol and −2.6 mmol/mol points, respectively. The analysis predicted HbA1c to be the lowest at 6 to 10 months post intensification, depending on intensification treatment and HbA1c at intensification; however, on average, HbA1c remained above 64.0 mmol/mol (8.0%). Conclusion In patients with T2DM, intensification following an HbA1c value ≥53 mmol/mol (7.0%) while on two OADs was associated with a significant improvement in glycaemic control. Patients intensified with insulin had a higher baseline HbA1c but greater HbA1c reduction than those intensified with a non‐insulin agent. However, HbA1c remained above 64 mmol/mol (8.0%) overall. Additional opportunity exists to further intensify therapy to improve glycaemic control.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Longitudinal changes in glycated haemoglobin following treatment intensification after inadequate response to two oral antidiabetic agents in patients with type 2 diabetes

Kim

Unni

Brixner

et al. 2019

“…Findings from the STENO‐2 study emphasized the importance of focusing on multifactorial risk reduction in T2DM management, on reduction of CV disease and renal impairment, as well as on improvement in treatment compliance in T2DM patients . Glycaemic control, weight loss and SBP reduction are known to markedly lower modifiable metabolic and CV‐related risk factors, and are recognized as valid composite endpoints in assessing T2DM management . In addition, changes in anthropometric measures are important and relevant to patients, and they have been associated with improvements in patient adherence to medication .…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Glycaemic control, weight loss and SBP reduction are known to markedly lower modifiable metabolic and CV-related risk factors, and are recognized as valid composite endpoints in assessing T2DM management. [30][31][32] In addition, changes in anthropometric measures are important and relevant to patients, and they have been associated with improvements in patient adherence to medication. 33,34 Over the 12-month study period, 40% of patients achieved the double composite endpoint and approximately 25% of patients achieved triple target control (Figure 3 Consistent with the safety findings observed in CANA clinical trials, [12][13][14][15][16][17][18] the overall incidence of AEs was low, with most being either mild or moderate in severity.…”

Section: Analyses Of Safetymentioning

confidence: 99%

CANadian CAnagliflozin REgistry: Effectiveness and safety of canagliflozin in the treatment of type 2 diabetes mellitus in Canadian clinical practice

Woo

Bell

Clement

et al. 2018

Aim There is limited information concerning the effects of canagliflozin (CANA), a sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) in a real‐world clinical setting in Canada. CanCARE is a 12‐month, prospective, observational analysis to demonstrate the effectiveness and safety of CANA in usual clinical practice in Canada. Materials and methods SGLT2i‐naïve adult patients with type 2 diabetes mellitus (T2DM) (n = 527) on a stable antihyperglycemic agent (AHA) regimen with glycated hemoglobin (A1C) ≥ 7%, an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 , were initiated on CANA as part of their usual treatment approach, and were followed for a period of 12 months. The primary effectiveness objective was the mean change in HbA1c from baseline to 6 and 12 months. Results Significant improvement from baseline in mean HbA1c levels were observed at 6 months (−0.90%; 95% CI, −1.02, −0.78) and at 12 months (−1.04%; 95% CI, −1.15, −0.92), regardless of duration of diabetes or background AHA treatment regimen. Similarly, significant decreases in systolic blood pressure (−4.65 mm Hg); body weight (−3.24 kg), waist circumference (−2.91 cm) and body mass index (−1.15 kg/m 2 ) were observed at 12 months. Additionally, 40.5% of patients achieved the double endpoint (≥0.5% HbA1c reduction and ≥ 3% weight loss), while 24.3% of patients achieved the triple composite endpoint (≥0.5% HbA1c reduction, ≥3% weight loss and ≥ 4 mm Hg systolic blood pressure reduction). No unexpected adverse events were reported. Conclusion CANA provided sustained clinically meaningful improvements in cardiometabolic parameters in this study in a real‐world setting, confirming findings from randomized controlled trials.

“…Treatment with iGlarLixi has been shown to achieve significantly greater reductions in HbA1c levels than iGlar alone . Although adherence to medication is a major determinant of glycaemic control in type 2 diabetes, real‐world data show that approximately 35% of patients discontinue treatment with GLP‐1RAs after 6 months . Therefore, the improved glycaemic control and reduced frequency/severity of GI AEs with iGlarLixi compared with alternatives showing higher rates of GI AEs may improve treatment adherence and outcomes.…”

Section: Discussionmentioning

confidence: 99%

Low incidence of gastrointestinal adverse events over time with a fixed‐ratio combination of insulin glargine and lixisenatide versus lixisenatide alone

Trujillo

Roberts

Dex

et al. 2018

This post hoc analysis of gastrointestinal (GI) adverse events (AEs) from the phase 3 LixiLan‐L (NCT02058160) and LixiLan‐O (NCT02058147) trials aimed to determine the frequency and timing of nausea, vomiting, and diarrhoea for iGlarLixi, a titratable, fixed‐ratio combination of insulin glargine 100 units/mL (iGlar) and lixisenatide, versus iGlar alone or iGlar and lixisenatide alone, in patients with type 2 diabetes uncontrolled with oral antidiabetes drugs (OADs) or basal insulin ± OADs. In iGlarLixi‐treated patients, the rate of GI AEs during the initial weeks of treatment was lower versus patients treated with lixisenatide alone (9.6% and 11.7% of iGlarLixi‐treated patients in LixiLan‐L and LixiLan‐O, respectively, vs. 27.5% of lixisenatide‐treated patients in LixiLan‐O). Beyond day 60, these rates were generally low and similar to those of lixisenatide. These lower rates are likely due to the gradual titration of lixisenatide in iGlarLixi. Median durations of intermittent GI AEs in the iGlarLixi arms were 6.0, 2.0 and 2.5 days (LixiLan‐L), and 5.0, 1.0 and 3.5 days (LixiLan‐O), respectively. iGlarLixi‐associated GI AEs were transient, mostly mild or moderate in severity, and occurred mainly during initial titration.