Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia.
OBJECTIVE
Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population.


METHODS
We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks.


RESULTS
HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% ± 0.12% with linagliptin/metformin (n = 132) and -2.02% ± 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to -0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference -0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred.


CONCLUSIONS
Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents.


BACKGROUND
www.clinicaltrials.gov identifier is NCT01512979.
a LMC Endocrinology Centres , University of Calgary , Calgary , Canada.
Stuart A
SA
Ross
b Joslin Diabetes Center , Harvard Medical School , Boston , MA , USA.
A Enrique
AE
Caballero
c Department of Endocrinology and Metabolism, Section of Diabetes , University of Pisa , Pisa , Italy.
Stefano
S
Del Prato
d Department of Medicine IV , Universitätsklinikum Tübingen , Tübingen , Germany.
Baptist
B
Gallwitz
e Boehringer Ingelheim Pharmaceuticals Inc , Ridgefield , CT , USA.
Diane
D
Lewis-D'Agostino
f Boehringer Ingelheim Ltd , Bracknell , UK.
Zelie
Z
Bailes
g Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany.
Sandra
S
Thiemann
f Boehringer Ingelheim Ltd , Bracknell , UK.
Sanjay
S
Patel
g Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany.
Hans-Juergen
HJ
Woerle
g Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany.
Maximilian
M
von Eynatten
D000328:Adult; D000368:Aged; D001786:Blood Glucose; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007677:Kidney Function Tests; D000069476:Linagliptin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D044469:Racial Groups
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin
Diabetes mellitus type 2; clinical trial; dipeptidyl peptidase 4 inhibitors; drug therapy combination; linagliptin; metformin