16 research outputs found
How to Care for Orphaned Wild Mammals
The following information has been derived from the experiences of wildlife rehabilitations specialists, as well as from journals on this topic. Itis important to note thatinformation must be adapted to accomodate the individual animal and consultation with a veterinarian is recommended. This is the first of a two-part series of articles
How to Care for Orphaned Wild Mammals Part II
The following information has been derived from the experiences of wildlife rehabilitations specialists, as well as from journals on this topic. It is important to note that information must be adapted to accommodate the individual animal and consultation with a veterinarian is recommended. This is the second of a two part series of articles on the care of orphaned wild mammals. Part I covered general information, and the care of cottontail rabbits and squirrels
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
How to Care for Orphaned Wild Mammals
The following information has been derived from the experiences of wildlife rehabilitations specialists, as well as from journals on this topic. Itis important to note thatinformation must be adapted to accomodate the individual animal and consultation with a veterinarian is recommended. This is the first of a two-part series of articles.</p
How to Care for Orphaned Wild Mammals Part II
The following information has been derived from the experiences of wildlife rehabilitations specialists, as well as from journals on this topic. It is important to note that information must be adapted to accommodate the individual animal and consultation with a veterinarian is recommended. This is the second of a two part series of articles on the care of orphaned wild mammals. Part I covered general information, and the care of cottontail rabbits and squirrels.</p
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Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials
To evaluate the safety and efficacy of empagliflozin 10- and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D).
The EASE (Empagliflozin as Adjunctive to inSulin thErapy) program (
= 1,707) included two double-blind, placebo-controlled phase 3 trials: EASE-2 with empagliflozin 10 mg (
= 243), 25 mg (
= 244), and placebo (
= 243), 52-week treatment; and EASE-3 with empagliflozin 2.5 mg (
= 241), 10 mg (
= 248), 25 mg (
= 245), and placebo (
= 241), 26-week treatment. Together they evaluated empagliflozin 10 mg and 25 mg, doses currently approved in treatment of type 2 diabetes, and additionally 2.5 mg on 26-week change in glycated hemoglobin (primary end point) and weight, glucose time-in-range (>70 to ≤180 mg/dL), insulin dose, blood pressure, and hypoglycemia.
The observed largest mean placebo-subtracted glycated hemoglobin reductions were -0.28% (95% CI -0.42, -0.15) for 2.5 mg, -0.54% (-0.65, -0.42) for 10 mg, and -0.53% (-0.65, -0.42) for 25 mg (all
< 0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by -1.8/-3.0/-3.4 kg (all
< 0.0001); increased glucose time-in-range by +1.0/+2.9/+3.1 h/day (
< 0.0001 for 10 and 25 mg); lowered total daily insulin dose by -6.4/-13.3/-12.7% (all
< 0.0001); and decreased systolic blood pressure by -2.1/-3.9/-3.7 mmHg (all
< 0.05). Genital infections occurred more frequently on empagliflozin. Adjudicated diabetic ketoacidosis occurred more with empagliflozin 10 mg (4.3%) and 25 mg (3.3%) but was comparable between empagliflozin 2.5 mg (0.8%) and placebo (1.2%). Severe hypoglycemia was rare and frequency was similar between empagliflozin and placebo.
Empagliflozin improved glycemic control and weight in T1D without increasing hypoglycemia. Ketoacidosis rate was comparable between empagliflozin 2.5 mg and placebo but increased with 10 mg and 25 mg. Ketone monitoring for early ketoacidosis detection and intervention and lower empagliflozin doses may help to reduce this risk
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1199-P: Analysis of Patient Preferences for Adjunct Therapy to Insulin in T1D
Recent ADA/EASD recommendations emphasize the importance of the patient role in therapy decisions. Adjunct to insulin SGLT inhibitor (SGLTi) therapy for T1D has been evaluated in RCTs but patient reaction to the benefit-risk profile of these agents is unknown. We aimed to objectively evaluate patient preferences for different therapy options, using a Discrete Choice Experiment (DCE) form of conjoint analysis, a validated methodology. The DCE used an online survey, completed by 701 respondents with T1D (231 U.S., 242 Canada, 228 Germany), to present 6 hypothetical, masked pair-wise drug profile comparison choices composed of different benefit-risk attributes and clinical effect ranges (levels). Attributes and levels were derived from different combinations of phase 3 trial data for a low dose SGLTi (comparable to empagliflozin 2.5mg); a high dose SGLTi (comparable to sotagliflozin 400mg); and an available adjunct to insulin therapy (pramlintide 60µg TID). Based upon respondents’ choices, DCE calculated, in %, the relative importance of one attribute to another and the overall predicted therapy preferences. DKA risk was the most important attribute with a relative importance of 23% (z-test, p<0.05). Second and similarly important were HbA1c reduction (14%), risk of hypoglycemia (13%), oral vs. injection treatment (13%), and risk of genital infection (12%). Next was risk of nausea (11%); weight reduction (8%) and risk of diarrhea (7%) were least important. The predicted therapy preference share was highest for low dose SGLTi, ranked first by 83% (z-test, p<0.05), compared with 8% for high dose SGLTi and 9% for pramlintide. In a separate question, respondents were asked to explicitly choose (masked to drug profile name and dose) among the clinical trial profiles of low dose SGLTi (chosen by 69%), high dose SGLTi (17%), pramlintide (6%), and ‘none of the above’ (9%).
In conclusion, the DCE and head-to-head explicit choice identified low dose SGLTi as the favored patient preference for adjunct therapy to insulin in T1D.
Disclosure
B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck & Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. L.M. Laffel: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Janssen Pharmaceuticals, Inc., UpToDate. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. C. Mathieu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S, Sanofi. C. Pang: Consultant; Self; dQ&A Market Research, Inc. R. Wood: Other Relationship; Self; Multiple companies in the diabetes field (>10 companies). O. Kinduryte: Employee; Self; Boehringer Ingelheim International GmbH. Stock/Shareholder; Self; Novo Nordisk A/S, Zealand Pharma A/S. J. George: Employee; Self; Boehringer Ingelheim International GmbH. J. Marquard: Employee; Self; Boehringer Ingelheim International GmbH. N. Soleymanlou: Employee; Self; Boehringer Ingelheim Canada Ltd.
Funding
Boehringer Ingelheim; Eli Lilly and Compan
Exploring Patient Preferences for Adjunct-to-Insulin Therapy in Type 1 Diabetes
OBJECTIVE: While sodium-glucose cotransporter inhibitor (SGLTi) therapy has been evaluated in type 1 diabetes (T1D) trials, patient reactions to benefits and risks are unknown. Using established methodology, we evaluated patient preferences for different adjunct-to-insulin therapy options in T1D. RESEARCH DESIGN AND METHODS: An online survey, completed by 701 respondents with T1D (231 U.S., 242 Canada, and 228 Germany), used conjoint analysis to present six hypothetical, masked, pairwise drug profile choices composed of different benefit-risk attributes and effect ranges. Data used in analyses were derived from actual phase 3 trials of a low-dose SGLTi (comparable to oral empagliflozin 2.5 mg q.d.), a high-dose SGLTi (comparable to oral sotagliflozin 400 mg q.d.), and an available adjunct-to-insulin therapy (comparable to subcutaneous pramlintide 60 μg t.i.d.). RESULTS: Conjoint analysis identified diabetic ketoacidosis risk as most important to patients (23% relative score; z test, P < 0.05); ranked second were HbA1c reduction (14%), risk of severe hypoglycemia (13%), oral versus injectable treatment (12%), and risk of genital infection (12%). Next was risk of nausea (11%), followed by weight reduction (8%) and the risk of diarrhea (7%). A low-dose SGLTi drug profile was identified by conjoint analysis as the top patient preference (83% of participants; z test, P < 0.05) versus high-dose SGLTi (8%) or pramlintide (9%). Separate from conjoint analysis, when respondents were asked to choose their preferred adjunct-to-insulin therapy (masked to drug name/dose), 69%, 17%, 6%, and 9% of respondents chose low-dose SGLTi, high-dose SGLTi, pramlintide, and insulin therapy alone, respectively. CONCLUSIONS: Low-dose SGLTi profile was the favored adjunct-to-insulin therapy by persons with T1D.status: publishe
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Exploring Patient Preferences for Adjunct-to-Insulin Therapy in Type 1 Diabetes
While sodium-glucose cotransporter inhibitor (SGLTi) therapy has been evaluated in type 1 diabetes (T1D) trials, patient reactions to benefits and risks are unknown. Using established methodology, we evaluated patient preferences for different adjunct-to-insulin therapy options in T1D.
An online survey, completed by 701 respondents with T1D (231 U.S., 242 Canada, and 228 Germany), used conjoint analysis to present six hypothetical, masked, pairwise drug profile choices composed of different benefit-risk attributes and effect ranges. Data used in analyses were derived from actual phase 3 trials of a low-dose SGLTi (comparable to oral empagliflozin 2.5 mg q.d.), a high-dose SGLTi (comparable to oral sotagliflozin 400 mg q.d.), and an available adjunct-to-insulin therapy (comparable to subcutaneous pramlintide 60 μg t.i.d.).
Conjoint analysis identified diabetic ketoacidosis risk as most important to patients (23% relative score;
test,
< 0.05); ranked second were HbA
reduction (14%), risk of severe hypoglycemia (13%), oral versus injectable treatment (12%), and risk of genital infection (12%). Next was risk of nausea (11%), followed by weight reduction (8%) and the risk of diarrhea (7%). A low-dose SGLTi drug profile was identified by conjoint analysis as the top patient preference (83% of participants;
test,
< 0.05) versus high-dose SGLTi (8%) or pramlintide (9%). Separate from conjoint analysis, when respondents were asked to choose their preferred adjunct-to-insulin therapy (masked to drug name/dose), 69%, 17%, 6%, and 9% of respondents chose low-dose SGLTi, high-dose SGLTi, pramlintide, and insulin therapy alone, respectively.
Low-dose SGLTi profile was the favored adjunct-to-insulin therapy by persons with T1D