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1.
J Emerg Med ; 52(2): 223-226, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27717592

RESUMEN

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. Acetone is one of the three main ketone bodies formed during DKA and it may be present at considerable concentrations, contributing to the serum osmolality.


Asunto(s)
Acetona/análisis , Cetoacidosis Diabética/diagnóstico , Transportador 2 de Sodio-Glucosa/agonistas , Acetona/sangre , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Glucemia/análisis , Canagliflozina/efectos adversos , Canagliflozina/uso terapéutico , Complicaciones de la Diabetes , Femenino , Humanos , Insulina/farmacología , Insulina/uso terapéutico , Metformina/farmacología , Metformina/uso terapéutico , Persona de Mediana Edad , Transportador 2 de Sodio-Glucosa/uso terapéutico
2.
Endocrine ; 55(1): 173-178, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27696231

RESUMEN

Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre. Out of 79 patients on this combination regimen with other anti-diabetic medications, 37 cases who had follow up at 3-6 months were studied. Mean age and duration of follow up were 57.4 (+/-7.8) and 139 (+/-32.6) days, respectively. Twenty-two patients (59.5 %) were Asians. Statistically significant improvements in clinical parameters such as body weight reduction (3.07 kg), glycated haemoglobin (HbA1c) reduction (1.05 %), lower BMI (-1.13 kg/M2) and insulin dose reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination regimen. Linear regression analysis showed that baseline HbA1c and baseline insulin dose were independent predictors of HbA1c reduction and insulin dose reduction, respectively. Our results suggest that combination therapy with GLP-1 agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/administración & dosificación , Obesidad/tratamiento farmacológico , Transportador 2 de Sodio-Glucosa/agonistas , Pérdida de Peso/efectos de los fármacos , Anciano , Glucemia , Diabetes Mellitus Tipo 2/etiología , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/uso terapéutico , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento
4.
J Clin Pharmacol ; 55(6): 647-56, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25612234

RESUMEN

Canagliflozin (INVOKANA™) is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Canagliflozin inhibits renal sodium-glucose co-transporter 2 (SGLT2), thereby, reducing reabsorption of filtered glucose and increasing urinary glucose excretion. Given the mechanism of action of SGLT2 inhibitors, we assessed the interplay between renal function, efficacy (HbA1c reduction), and safety (renal adverse reactions). The focus of this article is to highlight the FDA's quantitative clinical pharmacology analyses that were conducted to support the regulatory decision on dosing in patients with renal impairment (RI). The metrics for assessment of efficacy for T2DM drugs is standard; however, there is no standard method for evaluation of renal effects for diabetes drugs. Therefore, several analyses were conducted to assess the impact of canagliflozin on renal function (as measured by eGFR) based on available data. These analyses provided support for approval of canagliflozin in T2DM patients with baseline eGFR ≥ 45 mL/min/1.73 m(2) , highlighting a data-driven approach to dose optimization. The availability of a relatively rich safety dataset (ie, frequent and early measurements of laboratory markers) in the canagliflozin clinical development program enabled adequate assessment of benefit-risk balance in various patient subgroups based on renal function.


Asunto(s)
Canagliflozina/efectos adversos , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/metabolismo , Transportador 2 de Sodio-Glucosa/agonistas , Adulto , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Canagliflozina/administración & dosificación , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Relación Dosis-Respuesta a Droga , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Riñón/efectos de los fármacos , Farmacología Clínica/métodos , Insuficiencia Renal/sangre
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