Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: A 24-week, randomized, placebo-controlled study (GetGoal-Duo 1)
Riddle M.C.,Oregon Health And Science University |
Forst T.,Institute for Clinical Research and Development |
Aronson R.,LMC Diabetes & Endocrinology |
Sauque-Reyna L.,Institute Diabetes Obesidad y Nutricion Sociedad Civil |
And 4 more authors.
Diabetes Care | Year: 2013
OBJECTIVE-When oral therapy for type 2 diabetes is ineffective, adding basal insulin improves glycemic control. However, when glycated hemoglobin (HbA1c) remains elevated because of postprandial hyperglycemia, the next therapeutic step is controversial.We examined the efficacy and safety of lixisenatide in patients with HbA1c still elevated after initiation of insulin glargine. RESEARCH DESIGN AND METHODS-This double-blind, parallel-group trial enrolled patients with HbA1c 7-10% despite oral therapy. Insulin glargine was added and systematically titrated during a 12-week run-in, after which candidates with fasting glucose ≤7.8 mmol/L and HbA 1c 7-9% were randomized to lixisenatide 20 μg or placebo for 24 weeks while insulin titration continued. The primary end point was HbA 1c change after randomization. RESULTS-The randomized population (n = 446) had mean diabetes duration of 9.2 years, BMI 31.8 kg/m2, and daily glargine dosage of 44 units. HbA1c had decreased during run-in from 8.6 to 7.6%; adding lixisenatide further reduced HbA1c by 0.71 vs. 0.40% with placebo (least squares mean difference, -0.32%; 95% CI, -0.46 to -0.17; P < 0.0001). More participants attained HbA1c <7% with lixisenatide (56 vs. 39%; P < 0.0001). Lixisenatide reduced plasma glucose 2 h after a standardized breakfast (difference vs. placebo -3.2 mmol/L; P < 0.0001) and had a favorable effect on body weight (difference vs. placebo -0.89 kg; P = 0.0012). Nausea, vomiting, and symptomatic hypoglycemia <3.3 mmol/L were more common with lixisenatide. CONCLUSIONS-Adding lixisenatide to insulin glargine improved overall and postprandial hyperglycemia and deserves consideration as an alternative to prandial insulin for patients not reaching HbA1c goals with recently initiated basal insulin. © 2013 by the American Diabetes Association.
Reznik Y.,University of Caen Lower Normandy |
Cohen O.,Institute of Endocrinology |
Aronson R.,LMC Diabetes & Endocrinology |
Conget I.,University of Barcelona |
And 3 more authors.
The Lancet | Year: 2014
Background Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise). Methods We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8 0-12 0% (64-108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0 75 and size 4 with probability 0 25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01182493. Findings 495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1 1% (SD 1 2; 12 mmol/mol, SD 13) in the pump treatment group and 0 4% (SD 1 1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of -0 7% (95% CI -0 9 to -0 4; -8 mmol/mol, 95% CI -10 to -4, p<0 0001). At the end of the study, the mean total daily insulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (p<0 0001), with no significant difference in bodyweight change between the two groups (1 5 kg [SD 3 5] vs 1 1 kg [3 6], p=0 322). Two diabetes-related serious adverse events (hyperglycaemia or ketosis without acidosis) resulting in hospital admission occurred in the pump treatment group compared with one in the multiple daily injection group. No ketoacidosis occurred in either group and one episode of severe hypoglycaemia occurred in the multiple daily injection group. Interpretation In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option.
News Article | November 30, 2016
TORONTO--(BUSINESS WIRE)--#a1c--LMC Diabetes & Endocrinology, North America’s largest diabetes specialist care provider, has published a landmark study demonstrating the impact of its comprehensive, patient-centred care approach. The study, titled “DROP A1C”, was recently published in Diabetes Care, a peer-reviewed journal published by the American Diabetes Association. (http://care.diabetesjournals.org/content/early/2016/08/09/dc15-2666) The objective of the study was to determine if functionall
News Article | December 7, 2016
WASHINGTON, Dec. 7, 2016 /PRNewswire/ -- ViiMed®, a leading digital health platform, and LMC Diabetes & Endocrinology (LMC), the largest diabetes specialist care provider in North America, today announced a partnership to bring diabetes education and management programs to more than...
Aronson R.,LMC Diabetes & Endocrinology
Diabetes Technology and Therapeutics | Year: 2012
Despite the recognized importance of optimal insulin therapy, patient adherence to insulin therapy is an ongoing clinical care challenge. Insulin omission continues to be frequent and underestimated and has been correlated with poorer glycemic control and increased rates of diabetes-related complications. Insulin users consistently indentify multiple factors that contribute to insulin injection-related anxiety and to non-adherence. Injection-related discomfort continues to bear a significant contribution. Over the last decade, with advances in needle manufacturing technology, shorter and narrower needles have been associated with progressively improving patient self-rating of injection discomfort. Consequently, patient surveys of insulin users show discomfort to rank in the bottom third of significant contributors by prevalence. However, healthcare providers (HCP) and family member care providers continue to demonstrate a high level of anticipated and perceived pain for the patient. HCP anxiety and pain anticipation are each associated with patient anxiety and may therefore play a significant contributing role in patient non-adherence. © Copyright 2012, Mary Ann Liebert, Inc.
Aronson R.,LMC Diabetes & Endocrinology
Expert Review of Clinical Pharmacology | Year: 2013
Despite availability of new treatments for patients with Type 2 diabetes mellitus (T2DM), optimal management of glycemic control remains challenging. Treatment with basal insulin can improve HbA1c, but may not be sufficient to control postprandial plasma glucose (PPG) levels. Both fasting plasma glucose (FPG) and PPG levels contribute to overall glycemic control. In patients with moderate hyperglycemia, PPG excursions have a greater contribution to overall hyperglycemia, with this contribution being greatest when HbA1c is approximately 7-8% . Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been designed to restore and maintain GLP-1 levels and attenuate PPG excursions. GLP-1RAs that predominantly affect PPG may complement the FPG lowering provided by basal insulin, possibly improving overall glycemic control without additional weight gain and with limited incidence of hypoglycemia. Lixisenatide as an add-on to basal insulin lowers PPG levels, improves HbA1c control and has a beneficial effect on weight in T2DM patients. © 2013 Informa UK Ltd.
Aronson R.,LMC Diabetes & Endocrinology
Current Medical Research and Opinion | Year: 2015
Background: Treatment of type 2 diabetes mellitus invariably requires the use of multiple daily medications which can impact negatively on patient adherence. As a result, there is growing interest in the use of single-pill combinations that can reduce the pill burden. Many such formulations incorporate metformin, although this agent is not suitable for all patients. The single-pill combination of the dipeptidyl peptidase-4 inhibitor linagliptin with the sodium glucose co-transporter 2 inhibitor empagliflozin offers a new and attractive option, given their complementary mechanisms of action. Scope: Publications with titles containing the keywords 'linagliptin' or 'empagliflozin' were identified from a non-systematic search of PubMed without date restrictions, together with abstracts presented at the annual meetings of the American Diabetes Association and the European Association for the Study of Diabetes 2012-2014. ClinicalTrials.gov was searched for entries containing these two keywords. Additional references known to the author were included. Findings: The efficacy and safety of linagliptin and empagliflozin as monotherapy or in combination with other oral antidiabetic drugs has been established through extensive clinical trial programs. Studies specifically evaluating the efficacy/safety of a dipeptidyl peptidase-4 inhibitor/sodium glucose co-transporter 2 inhibitor in combination are limited, but do include two studies of linagliptin/empagliflozin of up to 52 weeks in duration. These studies show that the single-pill combination of linagliptin and empagliflozin produced clinical improvements in glycemic control that were generally superior to the improvements seen with linagliptin and empagliflozin alone, but with a safety profile comparable to that of the individual constituents. Conclusions: The single-pill combination of linagliptin and empagliflozin, with their complementary mechanisms of action, is a promising treatment option for patients with type 2 diabetes mellitus. It would reduce the daily pill burden in this population, potentially improving adherence to, and optimizing the benefits of, treatment of diabetes mellitus. © 2015 All rights reserved: reproduction in whole or part not permitted.
Ahren B.,Lund University |
Dimas A.L.,Research Center Clinica Del Pacifico |
Miossec P.,Sanofi S.A. |
Saubadu S.,Sanofi S.A. |
Aronson R.,LMC Diabetes & Endocrinology
Diabetes Care | Year: 2013
OBJECTIVE-To examine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone. RESEARCH DESIGN AND METHODS-This was a 24-week, randomized, doubleblind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7-10% [53-86 mmol/mol]). Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections. RESULTS-Lixisenatide morning injection significantly reduced mean HbA1c versus combined placebo (mean change -0.9% [9.8 mmol/mol] vs. -0.4% [4.4 mmol/mol]; least squares [LS] mean difference vs. placebo -0.5% [5.5 mmol/mol], P < 0.0001). HbA 1c was significantly reduced by lixisenatide evening injection (mean change -0.8% [8.7 mmol/mol] vs. -0.4% [4.4 mmol/mol]; LS mean difference -0.4% [4.4 mmol/mol], P < 0.0001). Lixisenatide morning injection significantly reduced 2-h postprandial glucose versus morning placebo (mean change -5.9 vs. -1.4 mmol/L; LS mean difference -4.5 mmol/L, P < 0.0001). LS mean difference in fasting plasma glucose was significant in both morning (-0.9 mmol/L, P < 0.0001) and evening (-0.6 mmol/L, P = 0.0046) groups versus placebo. Mean body weight decreased to a similar extent in all groups. Rates of adverse events were 69.4%in both lixisenatide groups and 60.0%in the placebo group. Rates for nausea and vomiting were 22.7 and 9.4% for lixisenatide morning and 21.2 and 13.3% for lixisenatide evening versus 7.6 and 2.9% for placebo, respectively. Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes. CONCLUSIONS-In patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated. © 2013 by the American Diabetes Association.
Goldenberg R.,LMC Diabetes & Endocrinology
Current Medical Research and Opinion | Year: 2014
Background: Insulin and incretin agents (dipeptidyl peptidase-4 inhibitors [DPP4is] and glucagon-like peptide-1 receptor agonists [GLP1 RAs]) are second-line treatment options in patients with type 2 diabetes (T2D) not achieving glycemic targets with metformin. Combinations of insulin with incretin agents have been explored in randomized controlled trials (RCTs) and retrospective studies. However, the optimal approach is still elusive; numerous combination regimens can be envisioned, differing in composition and in order of addition. Scope: A systematic survey was conducted of RCTs testing insulin/DPP4i or insulin/GLP1 RA regimens. PubMed and other online databases were queried using 'insulin' and the names of all incretin agents available in Canada, along with 'combination', 'concomitant', 'concurrent', and 'add-on'. Web of Science and clinicaltrials.gov were searched to identify unpublished trials. Findings: Fifteen placebo-controlled or active-comparator RCTs were identified, reporting outcomes for regimens combining insulins and incretin agents available in Canada. DPP4i add-on to insulin therapy (six trials) leads to modest A1c lowering, with weight neutrality. GLP1 RA and insulin combination therapy (GLP1 RA add-on, five trials; insulin add-on, two trials) is associated with significant A1c lowering, with beneficial effects on body weight. A single proof-of-concept trial compared GLP1 RA to DPP4i add-on to insulin, and only one RCT examined simultaneous introduction of an incretin agent with insulin. Adding an incretin agent to established basal insulin therapy may represent a useful alternative to insulin intensification with prandial or premixed insulin. Initial introduction of an incretin agent, with subsequent introduction of insulin, offers potential practical advantages. No study directly comparing order of addition has yet been reported. Conclusions: Insulin/incretin combination therapy comprises a variety of efficacious, weight-sparing regimens and may be considered for many patients who do not achieve glycemic targets when treated with insulin or an incretin agent. © 2014 Informa UK Ltd.
News Article | March 12, 2015
TORONTO--(BUSINESS WIRE)--LMC Diabetes & Endocrinology (LMC) and Manna Research are pleased to announce the merger of their research operations creating one of the largest networks of fully-owned and integrated outpatient clinical research sites in North America. LMC has built a global reputation by offering leading sites for diabetes and obesity research and conducting top quality research that is paired with the largest group of endocrinologists worldwide. LMC currently has nine clinical practices and research sites across Quebec, Ontario and Alberta. Manna Research works in clinical research across all areas of primary care and has four sites across Canada “The merger of LMC and Manna offers pharmaceutical and biotechnology sponsors unparalleled access to high quality research sites in Canada,” said Dr. Ronnie Aronson, chief medical officer of LMC. The two companies will still operate under their respective brands as LMC Diabetes & Endocrinology Research and Manna Research maintain their focus in their respective areas of expertise. “LMC and Manna are each leaders in the industry for their recruitment of patients and quality of data,” said Karri Venn, director of research at LMC. “We have already started streamlining best practices of both organizations and integrating the quality systems built on an extensive history of regulatory and sponsor inspections.” LMC also offers in-patient-clinical pharmacology (Phase I) studies in its state-of-the art facility in Toronto. “The expertise that LMC has shown in performing clinical pharmacology studies in diabetic patients can now be augmented by the experience that Manna has in running primary care studies,” said Dr. Graham Wood, president of research at Manna. “The LMC facility, experience of the staff and access to primary care patients offered by Manna allows us to offer one of the best clinical pharmacology units in North America for patient-based studies.” About LMC Diabetes & Endocrinology Founded by Dr. Ronnie Aronson in 1997, LMC Diabetes & Endocrinology is Canada’s leading national diabetes, endocrinology and metabolic disease practice, serving Canadian patients with diabetes and other general endocrinology concerns. LMC’s national practice is led by 33 endocrinologists in nine clinics in Ontario, Alberta and Quebec. LMC’s 160+ member team of healthcare professionals provide multidisciplinary community-based care to Canadian diabetics and endocrinology patients with a focus on education, service excellence and meeting their comprehensive medical needs. The team also operates full-service pharmacies and an online platform for diabetes education, material and supplies at http://www.diabetessource.ca/. LMC stands among global leaders in early through late stage endocrinology and metabolic disease clinical research, with nine Canadian sites and a dedicated Phase I research facility in Toronto. LMC has consistently been recognized among Canada’s Best Workplaces® by the Great Place to Work Institute. About Manna Research Manna Research is Canada’s leading group of fully owned primary care clinical investigator sites. Headquartered in Montreal, Manna Research has been conducting clinical studies since 1996 and is now operating in Toronto, Vancouver, Quebec City and Montreal. Manna consistently delivers its clients quality data and simplifies the clinical research process by providing a trusted end-to-end solution that encompasses centralized feasibility and contracts and utilizes a set of standard operating procedures across all sites.