Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin.
OBJECTIVE
Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment.


METHODS
This international, multi-centre, randomized, parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov NCT00855166) enrolled patients with T2DM (women 55-75 years and men 30-75 years; HbA1c 6.5-8.5%; BMI ≥ 25 kg/m(2) ; body weight ≤ 120 kg) whose T2DM was inadequately controlled on metformin. One hundred and eighty-two patients were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 50, serum markers of bone formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C-terminal cross-linking telopeptides of type I collagen; CTX), bone mineral density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA) measurements and adverse events of fracture were evaluated as safety objectives.


RESULTS
One hundred and sixty-five patients (90.7%) completed the first 50 weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX or BMD were identified over 50 weeks of dapagliflozin treatment, with no significant treatment-by-gender interactions. No fractures were reported.


CONCLUSIONS
Dapagliflozin had no effect on markers of bone formation and resorption or BMD after 50 weeks of treatment in both male and post-menopausal female patients whose T2DM was inadequately controlled on metformin.
Osteoporosis Research Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. osten.ljunggren@medsci.uu.se
Ö
Ö
Ljunggren
J
J
Bolinder
L
L
Johansson
J
J
Wilding
A M
AM
Langkilde
C D
CD
Sjöström
J
J
Sugg
S
S
Parikh
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin; D008687:Metformin