OBJECTIVE—Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS—This 28-week parallel-group study randomized 233 insulin-naive patients with HbA1c values ≥8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5–6 units BIAsp 70/30 twice daily or 10–12 units glargine at bedtime and titrated to target blood glucose (80–110 mg/dl) by algorithm-directed titration. RESULTS—A total of 209 subjects completed the study. At study end, the mean HbA1c value was lower in the BIAsp 70/30 group than in the glargine group (6.91 ± 1.17 vs. 7.41 ± 1.24%, P < 0.01). The HbA1c reduction was greater in the BIAsp 70/30 group than in the glargine group (−2.79 ± 0.11 vs. −2.36 ± 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA1c >8.5% (−3.13 ± 1.63 vs. −2.60 ± 1.50%, respectively; P < 0.05). More BIAsp 70/30–treated subjects reached target HbA1c values than glargine-treated subjects (HbA1c ≤6.5%: 42 vs. 28%, P < 0.05; HbA1c <7.0%: 66 vs. 40%, P < 0.001). Minor hypoglycemia (episodes/year) was greater in the BIAsp 70/30 group than in the glargine group (3.4 ± 6.6 and 0.7 ± 2.0, respectively; P < 0.05). Weight gain and daily insulin dose at study end were greater for BIAsp 70/30–treated subjects than for glargine-treated subjects (weight gain: 5.4 ± 4.8 vs. 3.5 ± 4.5 kg, P < 0.01; insulin dose: 78.5 ± 39.5 and 51.3 ± 26.7 units/day, respectively). CONCLUSIONS—In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA1c targets than once-daily glargine, especially in subjects with HbA1c >8.5%.
Summary. Insulin secretory responses to paired intravenous and oral glucose loads were determined in 38 nonobese individuals classified as normal (nondiabetic) subjects, "mild" diabetics (fasting blood glucose below 105 mg per 100 ml), or "moderate" diabetics (fasting glucose below 192 mg per 100 ml). Studies were also performed in 29 obese persons who were similarly grouped. The intravenous load was given to assess the alacrity of hormonal release after glycemic stimulus, and the oral glucose to determine how the speed of initial insulinogenesis modifies the disposition of ingested carbohydrate.In the nonobese group, normal subjects responded to massive hyperglycemia after rapid injection of glucose with immediate and maximal outpouring of insulin, in contrast to a desultory insulinogenic response in patients with mild diabetes, and no initial response at all in moderate diabetics. During oral glucose tolerance tests, the much faster clearance of blood sugar in nondiabetic subjects was actually associated with lower absolute insulin output than was found in mildly diabetic patients, since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia. Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia. An empirical "insulinogenic index," the ratio relating enhancement of circulating insulin to magnitude of corresponding glycemic stimulus, was used to compare the secretory capacities of respective groups. Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great. This relatively greater normal secretory response declared itself shortly after the administration of glucose by either route, and was maintained throughout both tests.In the 29 obese individuals, differences among groups were essentially the same as in persons of normal weight. Obese nondiabetics did show much larger absolute insulinogenic responses during both tests than did nonobese controls. Since corresponding glucose tolerance curves were also higher, the mean insulinogenic indexes for obese subjects were not statistically greater. Moreover, when comparable glucose curves of obese and nonobese controls * Submitted for publication September 13, 1965; ac- were matched, the apparent hyperinsulinemia associated with obesity was again reduced to insignificance. At the same time, a tendency toward perpetuation of higher insulin levels in overweight normal subjects and mild diabetics, in response to both glucose loads, suggested that obesity per se does induce a state of peripheral insulin resistance.The data indicate that normal beta cells respond instantly to a glycemic stimulus, whereas diabetic islets react sluggishly, and that proportionally greater insulinogenesis accounts for faster disposal of postprandial hyperglycemia in nondiabetics than in diabetics, in both nonobese and obese individuals. By tracing a rational sequence of events within the beta cell-fro...
Aim:The study aim was to evaluate the efficacy and safety of initial combination therapy with saxagliptin þ metformin vs. saxagliptin or metformin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control. Methods: In this multicentre, randomized, double-blind, active-controlled phase 3 trial, 1306 treatment-naïve patients with T2D !18 to 77 years, glycosylated haemoglobin (HbA1c) !8 to 12%, fasting C-peptide concentration !1.0 ng/ml, body mass index 40 kg/m 2 were randomized to receive saxagliptin 5 mg þ metformin 500 mg, saxagliptin 10 mg þ metformin 500 mg, saxagliptin 10 mg þ placebo or metformin 500 mg þ placebo for 24 weeks. From weeks 1-5, metformin was uptitrated in 500-mg/day increments to 2000 mg/day maximum in the saxagliptin 5 mg þ metformin, saxagliptin 10 mg þ metformin and metformin þ placebo treatment groups. The main outcome measure was HbA1c change from baseline to week 24. Selected secondary outcomes included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA1c <7% and postprandial glucose area under the curve (PPG-AUC).Results: At 24 weeks, saxagliptin 5 mg þ metformin and saxagliptin 10 mg þ metformin demonstrated statistically significant adjusted mean decreases vs. saxagliptin 10 mg and metformin monotherapies in HbA1c (À2.5 and À2.5% vs. À1.7 and À2.0%, all p < 0.0001 vs. monotherapy) and FPG (À60 and À62 mg/dl vs. À31 and À47 mg/dl, both p < 0.0001 vs. saxagliptin 10 mg; p ¼ 0.0002 saxagliptin 5 mg þ metformin vs. metformin; p < 0.0001 saxagliptin 10 mg þ metformin vs. metformin). Proportion of patients achieving an HbA1c <7% was 60.3 and 59.7%, respectively, for saxagliptin 5 mg þ metformin and saxagliptin 10 mg þ metformin (all p < 0.0001 vs. monotherapy). PPG-AUC was significantly reduced [À21 080 mgÁmin/dl (saxagliptin 5 mg þ metformin) and À21 336 mgÁmin/dl (saxagliptin 10 mg þ metformin) vs. À16 054 mgÁmin/dl (saxagliptin 10 mg) and À15 005 mgÁmin/dl (metformin), all p < 0.0001 vs. monotherapy]. Adverse event occurrence was similar across all groups. Hypoglycaemic events were infrequent. Conclusion: Saxagliptin þ metformin as initial therapy led to statistically significant improvements compared with either treatment alone across key glycaemic parameters with a tolerability profile similar to the monotherapy components.
Saxagliptin added to TZD provided statistically significant improvements in key parameters of glycemic control vs. TZD monotherapy and was generally well tolerated.
Aim: This observational study in patients with type 2 diabetes failing oral agent therapy with or without basal insulin was conducted to assess whether addition and self‐titration of biphasic insulin aspart 70/30 (BIAsp 30) could achieve American Association of Clinical Endocrinologists (AACE)/International Diabetes Federation (IDF) and American Diabetes Association (ADA) glycemic targets (HbA1c≤6.5 and <7%). Methods: Enrolled patients (n = 100, HbA1c≥7.5 and ≤10%) were ≥18 years of age, had diabetes ≥12 months and had received a stable antidiabetic regimen for at least 3 months [minimum of two oral antidiabetic drugs (OADs) or at least one OAD plus once‐daily basal insulin ≤60 U]. Patients discontinued prior basal insulin and added one injection of BIAsp 30 (12 U or 70–100% of prior basal insulin dose within 15 min of dinner initiation). Patients self‐titrated their BIAsp 30 dose with investigator guidance every 3 or 4 days to achieve pre‐breakfast fasting blood glucose (FBG) of 80–110 mg/dl. At 16 weeks, a pre‐breakfast injection of 6 U of BIAsp 30 was added if week 15 HbA1c exceeded 6.5%; the added dose was titrated to achieve pre‐dinner BG of 80–110 mg/dl. After an additional 16 weeks, 3 U of pre‐lunch BIAsp 30 was added if HbA1c exceeded 6.5%. This added dose was adjusted based on 2‐h post‐lunch BG to achieve postprandial glucose of 100–140 mg/dl. Subjects achieving an HbA1c≤6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively. Results: Addition of once‐daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA1c≤6.5%) and 41% to achieve ADA targets (HbA1c <7%). With two daily injections of BIAsp 30, these glycaemic goals were achieved by 52 and 70% of subjects. With three daily BIAsp 30 injections, 60% of patients achieved HbA1c≤6.5%, and 77% achieved HbA1c <7.0%. Conclusions: This clinical trial demonstrates that initiation of once‐daily BIAsp 30 to type 2 diabetes patients poorly controlled on various OAD regimens was an effective treatment approach for achieving glycaemic goals. Additional patients safely achieved these goals by increasing the number of BIAsp 30 injections from one to two, and then, if uncontrolled, from two to three doses per day. Eventually, most patients previously uncontrolled on OADs with or without basal insulin were controlled by the addition and vigorous titration of BIAsp 30 to oral agent therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.