No abstract

Dapagliflozin as adjunct therapy to adjustable insulin in patients with type 1 diabetes was well tolerated and improved glycemic control with no increase in hypoglycemia versus placebo but with more DKA events.

clinicaltrials.gov Identifier: NCT01923181.

OBJECTIVETo assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin. RESEARCH DESIGN AND METHODSIn this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallelgroup, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/ day) 6 metformin ( ‡1,500 mg/day). RESULTSBaseline HbA 1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA 1c levels (-0.5% [-4.9 . Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%). CONCLUSIONSThese results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.

Dermatologists may commonly see skin lesions that reflect an underlying endocrine disorder. Identifying the endocrinopathy is very important, so that patients can receive corrective rather than symptomatic treatment. Skin diseases with underlying endocrine pathology include: thyrotoxicosis; hypothyroidism; Cushing syndrome; Addison disease; acromegaly; hyperandrogenism; hypopituitarism; primary hyperparathyroidism; hypoparathyroidism; pseudohypoparathyroidism and manifestations of diabetes mellitus. Thyrotoxicosis may lead to multiple cutaneous manifestations, including hair loss, pretibial myxedema, onycholysis and acropachy. In patients with hypothyroidism, there is hair loss, the skin is cold and pale, with myxedematous changes, mainly in the hands and in the periorbital region. The striking features of Cushing syndrome are centripetal obesity, moon facies, buffalo hump, supraclavicular fat pads, and abdominal striae. In Addison disease, the skin is hyperpigmented, mostly on the face, neck and back of the hands. Virtually all patients with acromegaly have acral and soft tissue overgrowth, with characteristic findings, like macrognathia and enlarged hands and feet. The skin is thickened, and facial features are coarser. Conditions leading to hyperandrogenism in females present as acne, hirsutism and signs of virilization (temporal balding, clitoromegaly).A prominent feature of hypopituitarism is a pallor of the skin with a yellowish tinge. The skin is also thinner, resulting in fine wrinkling around the eyes and mouth, making the patient look older. Primary hyperparathyroidism is rarely associated with pruritus and chronic urticaria. In hypoparathyroidism, the skin is dry, scaly and puffy. Nails become brittle and hair is coarse and sparse. Pseudohypoparathyroidism may have a special somatic phenotype known as Albright osteodystrophy. This consists of short stature, short neck, brachydactyly and subcutaneous calcifications. Some of the cutaneous manifestations of diabetes mellitus include necrobiosis lipoidica diabeticorum, diabetic dermopathy, scleredema adultorum and acanthosis nigricans.