Clinical studies confirm linagliptin's efficacy and tolerability in combination therapy with metformin
BURLINGTON AND TORONTO, ON, June 27, 2011 /CNW/ - Boehringer Ingelheim
and Lilly today announced Phase III study results for linagliptin,
demonstrating improved glycemic control in adults with type 2 diabetes
(T2D) whose blood glucose is not adequately controlled on current
therapy. In one long-term study over two years evaluating linagliptin
or glimepiride when added to metformin, linagliptin was effective at
lowering blood glucose, as measured by haemoglobin A1C (A1C)**5 but with relative weight loss (-1.4 kg vs. +1.5 kg; adjusted mean
difference, -2.9 kg; p0.0001), reduced incidence of hypoglycaemia (7.5
per cent vs. 36.1 per cent; p0.0001) and few cardiovascular (CV) events
(1.5 per cent vs. 3.4 per cent; Relative Risk 0.46 [0.23-0.91] p=0.02).1 Results will be presented at the 71st Annual American Diabetes Association (ADA) Scientific Sessions in San
Diego, California from June 25 - 29, 2011.
"The combination of linagliptin plus metformin provides meaningful
glucose control comparable to that of a combination of a sulphonylurea
plus metformin. The added benefit is that, linagliptin is not
associated with weight gain and does not per se increase the occurrence
of hypoglycaemia" said Prof. Klaus Dugi, Corporate Senior Vice
President Medicine, Boehringer Ingelheim. "In addition, linagliptin was
associated with a 54 per cent relative risk reduction for
cardiovascular events in this study. This highlights the promising
cardiovascular safety data seen with linagliptin to date which we are
currently further exploring in the CAROLINA study."
Another study of 24-weeks duration evaluating linagliptin demonstrated
mean placebo-corrected A1C reductions of up to 1.7 per cent from
baseline when linagliptin 2.5 mg twice daily (bid) was used in
combination with metformin 1,000 mg bid in T2D patients with
insufficient glycemic control.2 The combination of linagliptin plus metformin was well tolerated and
improved glycemic control more than either medication when used alone.
In the trial, there was no weight gain with the linagliptin plus
metformin combination, and a very low risk of hypoglycaemia (five
cases, or 1.8 per cent of patients).2 In an open label arm including patients with poor glycemic control (A1C
at baseline >11 per cent) linagliptin 2.5 mg twice daily (bid) in
combination with metformin 1,000 mg bid achieved a reduction from
baseline of A1C of 3.7 per cent.2
Linagliptin was also evaluated in T2D patients with varying degrees of
renal function.3 A large pooled analysis of three randomised, placebo-controlled Phase
III trials (n=2,141) showed that patients who received linagliptin had
A1C reductions independent of their degree of renal function, with
placebo corrected mean -0.63 per cent (p0.0001) for those with normal
renal function and -0.69 per cent for those with mildly or moderately
impaired renal function (p0.0001, p=0.0174, respectively).3 In an additional study evaluating T2D patients with severe renal
impairment (RI) whose blood glucose was insufficiently controlled,
linagliptin provided placebo-corrected A1C reduction of -0.6 per cent
(p0.0001) after 12 weeks of treatment.4 Renal function remained stable over time and CV deaths in this
high-risk population were low: one patient per arm.4
About the Linagliptin Studies
Two year phase III study comparing linagliptin to glimepiride, add on to metformin
The aim of this two-year study was to assess the long-term efficacy and
safety profile of adding linagliptin or glimepiride to ongoing stable
metformin (greater than or equal to 1,500 mg/d for greater than or
equal to 10 weeks) to treat T2D in those who have not achieved glycemic
T2DM patients on stable metformin (1,500mg/d) for 10 weeks were
randomised to linagliptin 5mg/d (N=764) or glimepiride 1−4 mg/d (N=755)
over two years. The efficacy endpoint was the change in A1C from
baseline. Key secondary endpoints assessed the frequency of
hypoglycemic events and changes in body weight over time. Another
safety endpoint evaluated pre-specified, prospective and adjudicated
capture of CV events.
Combination with Metformin in T2D Patients (279-OR)2
The aim of this 24-week, study was to evaluate the combination of
linagliptin plus metformin in T2D patients with inadequate glycemic
The six treatment groups were randomised into combinations of
linagliptin 2.5 mg bid plus either low- or high-dose (500 or 1000 mg)
metformin bid, linagliptin 5 mg once daily (qd), metformin 500 or 1,000
mg bid, and placebo. Patients with a baseline A1C greater than or equal
to 11 per cent received open-label combination therapy with linagliptin
2.5 mg plus metformin 1,000 mg bid (n=66). Mean baseline A1C was
between 8.5 per cent and 8.7 per cent, and 11.8 per cent in the
open-label arm. Adverse event (AE) rates were similar across treatment
Efficacy and Safety in Patients with T2D with or Without RI (1068-P)3
The aim of this pooled analysis of three global studies was to evaluate
the effect of renal function on the efficacy and safety of linagliptin
in T2D patients with or without declining renal function.
The primary endpoint in all trials was the change in A1C from baseline
to week 24. The data assessed 2,141 patients with T2D who were grouped
by renal function as normal GFR greater than or equal to 80 mL/min,
n=1,684), mild RI (GFR, 50 to less than 80 mL/min, n=418), or moderate
RI (GFR, 30 to less than 50 mL/min, n=39).
Patients who received linagliptin showed consistent placebo-corrected
adjusted mean A1C changes across all three groups (-0.6 per cent in
both the normal and mild RI groups and -0.7 per cent in the moderate RI
The proportion of patients reporting a severe AE with linagliptin in the
normal/mild/moderate groups were 2.5 per cent, 5.4 per cent and 3.7 per
cent, respectively; and placebo was 3.4 per cent, 3.8 per cent, 8.3 per
Renal function, as assessed by Glomerular Filtration Rate (GFR), and the
urinary albumin/creatinine ratio (a surrogate for diabetic
nephropathy), was unaffected in all three groups after 24 weeks of
Safety and Efficacy in T2D Patients with Severe RI (413-PP)4
The aim of this study was to evaluate the effect of renal function on
the efficacy and safety of linagliptin in T2D patients (defined as A1C
greater than or equal to 7 per cent and less than or equal to 10 per
cent) and severe RI (defined as GFR less than 30 mL/min/1.73 m2).
The primary endpoint was the change in A1C from baseline to week 12. The
study assessed linagliptin 5 mg qd (n=68) vs. placebo (n=65) in
patients whose glucose-lowering background therapy remained unchanged
(insulin and/or sulphonylurea).
The change from baseline for all patients with linagliptin tablets 5 qd
was -0.8 per cent (n=66) and with placebo -0.2 per cent (n=62) p=
0.0001. The change from baseline in the subgroup of poorly controlled
patients (baseline A1C greater than or equal to 9 per cent) was -1.5
per cent with linagliptin 5 qd (n=11) and -0.3 per cent with placebo
(n=13), p= 0.0021.
The proportion of patients reporting an AE was 85.3 per cent for
linagliptin and 70.8 per cent for placebo, respectively. Hypoglycaemia
occurred in 51.5 per cent of linagliptin and 27.7 per cent of
placebo-treated patients. Notably, 61 of the 66 patients receiving
linagliptin were on their unchanged doses of insulin and/or
sulphonylurea background therapy. Renal function remained stable
throughout the study in both treatment arms and CV deaths in this
high-risk population were low: one patient per arm.
Type 2 Diabetes
There are approximately 285 million people with diabetes in the
population worldwide5 and over 9 million Canadians with diabetes or prediabetes.6 The Canadian Diabetes Association estimates that by 2020, it is
expected that 9.9 per cent of the population will be living with
diabetes.7 Type 2 diabetes usually occurs later in life and affects approximately
90 per cent of people with diabetes.8 The list of complications that diabetes patients face is long. In
Canada, diabetes is the single largest cause of blindness and 42 per
cent of new kidney dialysis patients in 2004 had diabetes.9
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company
announced an alliance in the field of diabetes that centres on four
pipeline compounds representing several of the largest treatment
classes. This alliance leverages the companies' strengths as two of the
world's leading pharmaceutical companies, combining Boehringer
Ingelheim's solid track record of research-driven innovation and
Lilly's innovative research, experience, and pioneering history in
diabetes. By joining forces, the companies demonstrate commitment in
the care of patients with diabetes and stand together to focus on
patient needs. Find out more about the alliance at www.boehringer-ingelheim.ca or www.lilly.com .
About Boehringer Ingelheim (Canada) Ltd.
The Boehringer Ingelheim group is one of the world's 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 145 affiliates and more than 42,000 employees.
Since it was founded in 1885, the family-owned company has been
committed to researching, developing, manufacturing and marketing novel
products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to
act socially responsible. Involvement in social projects, caring for
employees and their families, and providing equal opportunities for all
employees form the foundation of the global operations. Mutual
cooperation and respect, as well as environmental protection and
sustainability are intrinsic factors in all of Boehringer Ingelheim's
endeavors. In 2010, Boehringer Ingelheim posted net sales of 11.7
billion euro while spending almost 24 per cent of net sales in its
largest business segment Prescription Medicines on research and
The Canadian headquarters of Boehringer Ingelheim was established in
1972 and the Research and Development Centre located in Laval, Québec,
Canada since 1988. Boehringer Ingelheim (Canada) Ltd. is home to more
than 700 employees including 160 scientists across the country.
For more information please visit www.boehringer-ingelheim.ca
About Eli Lilly Canada Inc.
Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of first-in-class and best-in-class pharmaceutical products
by applying the latest research from its own worldwide laboratories and
from collaborations with eminent scientific organizations.
Headquartered in Indianapolis, Indiana, Lilly provides answers -
through medicines and information - for some of the world's most urgent
medical needs. Eli Lilly Canada, headquartered in Toronto, Ontario,
employs close to 500 people across the country. Additional information
about Eli Lilly Canada can be found at www.lilly.ca.
Gallwitz B, Uhlig-Laske B, Bhattacharaya S, et al. Linagliptin has
Similar Efficacy to Glimepiride but Improved Cardiovascular Safety over
2 Years in Patients with Type 2 Diabetes Inadequately Controlled on
Metformin 71th Scientific Sessions of the American Diabetes Association, San
Diego, California. 2011;Poster 39-LB.
Haak T, Meinicke T, Jones R, et al. Combination of Linagliptin and
Metformin Improves Glycemic Control in Type 2 Diabetes: A Randomized
Trial with an Open-Label Arm in Patients with Poor Glycemic Control. 71th Scientific Sessions of the American Diabetes Association, San
Diego, California. 2011;Oral presentation 279.
Cooper M, von Eynatten M, Emser A, et al. Efficacy and Safety of
Linagliptin in Patients With Type 2 Diabetes With or Without Renal
Impairment: Results from a Global Phase 3 Program. 71th Scientific Sessions of the American Diabetes Association, San
Diego, California. 2011;1068-P.
Sloan L, Newman J, Sauce C, et al. Safety and Efficacy of Linagliptin in
Type 2 Diabetes Patients with Severe Renal Impairment. 71th Scientific Sessions of the American Diabetes Association, San
Diego, California. 2011;Poster 413-PP.
* Linagliptin is an investigational compound and has not been approved
** Difference in mean A1C change from baseline between groups -0.20 per
cent; 95 per cent -CI, 0.11-0.29 per cent on a pre-specified
non-inferiority margin of 0.35 per cent
SOURCE Boehringer Ingelheim
For further information:
Boehringer Ingelheim (Canada) Ltd.
Phone: (905) 631-4713
Cell phone: (905) 599-2364
Eli Lilly Canada Inc.
Phone: (416) 693-3169
Cell phone: (416) 770-4962