IMPROVED METABOLIC CONTROL WITH A FAVORABLE WEIGHT PROFILE IN PATIENTS WITH TYPE 2 DIABETES TREATED WITH INSULIN GLARGINE (LANTUS®) IN CLINICAL PRACTICE STEPHAN A SCHREIBER AND ANIKA RUßMAN ABSTRACT Improving metabolic control without weight gain is a challenge in the management of Type 2 diabetes. In this open label, single center, nine-month study in clinical practice, the effect of insulin glargine (LANTUS®) on metabolic control and body weight was evaluated in 72 patients with Type 2 diabetes. Thirty-two insulin-naïve patients who were previously on oral antidiabetic medication were initiated on once-daily insulin glargine with either glimepiride (Amaryl®) or, in a few cases, glimepiride plus metformin, after participating in an educational program on insulin therapy. Forty patients treated previously with insulin were switched to once-daily insulin glargine plus mealtime regular human insulin or insulin lispro, after an educational program on intensified conventional therapy (ICT). Metabolic control and body weight were monitored for 9 months. In the 32 patients treated previously with oral agents, metabolic control improved significantly from baseline (HbA
decreased from 9.0% to 7.4%; p <0.005),
while body weight was reduced vs baseline. In the 40 patients treated previously with insulin, no statisticallysignificant change in body weight from baseline to endpoint was detected. HbA
patients who were previously on mixed insulin (–1.7%; p <0.04 vs baseline) and in the 15 patients on oral agentsplus NPH insulin (–1.5%; p <0.05 vs baseline). In patients previously on ICT (n=12), there was a trend towardsincreased HbA
(+0.5%). Overall, in the 72 patients examined in this study, there was a significant reduction in
from baseline to endpoint (8.14% to 7.58%; p <0.001). This was accompanied by slight weight reduction
(94.91 kg to 93.79 kg). In conclusion, insulin glargine in combination with glimepiride or prandial insulin improvesmetabolic control while showing a favorable weight profile, in patients with Type 2 diabetes.
INTRODUCTION ● The advent of insulin analogs is of major clinical significance in the treatment of diabetes1 ● Patients with Type 2 diabetes often benefit from approaches that aim to improve insulin sensitivity, such as weight
reduction through dietary modifications and exercise2. However, these approaches often do not lead to satisfactoryglycemic control and, consequently, pharmacologic therapy is required
● Improved metabolic control without weight gain is a challenge in the drug treatment of Type 2 diabetes, especially since
insulin therapy is often associated with weight gain
● Insulin glargine (LANTUS®) is a novel, long-acting human insulin analog, which has a smooth action profile with no
pronounced peak and a prolonged duration of action2 that makes it appropriate for once-daily use
● Once-daily insulin glargine is as effective as once or twice-daily NPH insulin in improving and maintaining glycemic
● Previous studies have demonstrated that insulin glargine improves metabolic control and has a favorable weight profile
and reduced incidence of nocturnal hypoglycemia in patients with Type 1 diabetes4 and Type 2 diabetes3,5,6
STUDY OBJECTIVES ● To evaluate the effect of insulin glargine combined with prandial insulin or oral hypoglycemic agents (OHAs) on
metabolic control and body weight in patients with Type 2 diabetes who had received pre-treatment with OHAs only, orpre-treatment with conventional insulin therapy or intensified conventional insulin therapy (ICT)
● To determine whether the efficacy variables were influenced by the type of insulin therapy that patients received prior
to commencing their insulin glargine regimen
● To improve patient education for self-management of insulin therapy and diet, in order to optimize glycemic control and
STUDY DESIGN AND METHODS Study design ● Single center, open-label, 9 month study carried out in a diabetes practice in Germany ● The study design is summarized in Figure 1 Insulin-naïve patients● Prior to initiating insulin glargine treatment, insulin-naïve patients (n=27) were divided into subgroups and received
insulin pre-treatment: 11 were pre-treated with OHAs plus insulin; 16 remained on OHAs only
● After participating in an educational program on insulin therapy and diet, these patients were initiated on once-daily
insulin glargine with one of the following therapies:– Glimepiride (Amaryl®) (n=21)– Glimepiride plus metformin (n=6)
Insulin-experienced patients● Prior to initiating insulin glargine treatment, insulin-experienced patients (n=33) were divided into subgroups and
received pre-treatment with ICT (n=23) or with conventional insulin therapy (n=10)
● After taking part in an educational program on ICT, these patients were switched to once-daily insulin glargine plus
mealtime regular human insulin or insulin lispro
Patients ● Patients with Type 2 diabetes (n=72) ● The data presented here refer only to those patients who received insulin glargine for 9 months (n=60) ● Patients who received insulin glargine for longer than nine months (n=12) have been excluded ● The dose of insulin glargine was titrated, whilst the dose of OHAs was kept stable Figure 1. Flow chart of patient recruitment and group assignment Previous treatment Previous treatment Pre-treatment subgroups Pre-treatment subgroups
ICT (n=23); Conventional treatment (n=10)
* Received insulin glargine for more than 9 months
Efficacy variables Metabolic control● Metabolic control was monitored at the start of the study (baseline) and after 9 months (endpoint) through
Body weight● Changes in body weight were monitored at baseline and endpoint
Safety measurements ● Severe hypoglycemia (requiring the assistance of a third party) was recorded; mild episodes were not recorded Statistical analysis ● All variables were analyzed using descriptive statistics RESULTS Patients ● Baseline characteristics of patients enrolled in the study are summarized in Table 1 Table 1. Baseline characteristics of patients Variable OHA pre-treatment Insulin only pre-treatment Efficacy Metabolic control ● In the 60 patients examined in this study, there was a significant reduction in HbA1c from baseline to endpoint (8.1%
● In the 27 patients pre-treated with OHAs, metabolic control improved significantly from baseline, as indicated by a
decrease in HbA of 1.5% (8.8% to 7.3%; p <0.01) (Figure 2)
● In the 33 patients pre-treated with insulin only, there was no change in HbA1c (Figure 2)
Figure 2. Reduction in mean HbA1c levels in patients with Type 2 diabetes treated with insulin glargine for 9 months (%) 1c HbA All subjects Insulin only Pre-treatment regimen Body weight● Following 9 months’ treatment with insulin glargine, in the 60 patients examined, there was a slight but detectable
reduction in body weight (94.9 kg to 93.8 kg) (Figure 3)
● At endpoint, a reduction in body weight was detected in the 27 patients pre-treated with OHAs (mean weight loss
1.1 kg) and in the 33 patients pre-treated with insulin only (mean weight loss 1.2 kg; Figure 3)
Figure 3. Reduction in body weight in patients with Type 2 diabetes treated with insulin glargine for 9 months Body weight (kg) All subjects Insulin only Pre-treatment regimen Efficacy Metabolic control: pre-treatment subgroups ● Following treatment with insulin glargine, HbA1c levels had altered as shown in Figure 4
● A reduction in HbA1c was detected in the subgroup of patients who were pre-treated with OHAs plus insulin (n=11;
● There was no significant change in HbA1c levels in the patients pre-treated with ICT (n=23) or in the patients pre-treated
Figure 4. Analysis of HbA1c levels at baseline and endpoint in the pre-treated insulin subgroups following insulin glargine treatment OHAs plus insulin Conventional therapy Type of insulin pre-treatment Body weight: pre-treatment subgroups● After switching to insulin glargine, there was a clear reduction in body weight in all patients who had received insulin
Figure 5. Analysis of body weight at baseline and endpoint in the pre-treated insulin subgroups following treatment with insulin glargine Body weight (kg) OHAs plus insulin Conventional therapy Type of insulin pre-treatment Safety ● No unexpected adverse events or episodes of severe hypoglycemia were reported CONCLUSIONS ● Overall, over a 9 month period, insulin glargine in combination with glimepiride (and metformin in a small proportion
of patients [n=6]), or prandial insulin, significantly improved metabolic control in patients with Type 2 diabetes, withoutincreasing body weight
● The favorable weight outcomes in this study could be attributed to the synergistic approach of providing dietary patient
education prior to insulin glargine treatment
Vaidyanathan B, Menon PS. Insulin analogues and management of diabetes mellitus. Indian J Pediatr 2000; 67(6): 435–441.
Mudaliar S, Edelman SV. Insulin therapy in type 2 diabetes. Endocrinol Metab Clin North Am 2001; 30(4): 935–982.
Rosenstock J, Schwartz S, Clark Jr C, Park G, Donley D, Edwards M. Basal insulin therapy in type 2 diabetes. Diabetes Care 2001; 24(4): 631–636.
Raskin P, Klaff L, Bergenstal R, Halle JP, Donley D, Mecca T. A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes. Diabetes Care 2000; 23(11): 1666–1671.
Yki-Järvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care 2000; 23(8): 1130–1136.
Rosenstock J, Schwartz S, Clark C, Edwards M, Donley D. Efficacy and safety of HOE 901 (insulin glargine) in subjects with type 2 DM: a 28-week randomized, NPH insulin- controlled trial. Diabetes 1999; 48(Suppl 1): Abstract 432.
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Case Report EXFOLIATIVE DERMATITIS DUE TO ETHAIVMBUTOL M.F.M. Miranda1, V.L Rege2 and V.E. Coelho3 (Received on 9.11.95; Accepted on 30.11.95) Summary: An unusual reaction to Ethamtautol change. There was no lymphadenopathy, and no manifesting as exfoliative dermatitis Is signs of pleurisy or pleural effusion. The other presented, The diagnosis was confirmed by syste