Insulin Analogues versus Pump Therapy in Type 2 Diabetes: Benefits from Pump Therapy Eric RENARD, MD, PhD Endocrinology Dept, Lapeyronie Hospital Montpellier, France e-renard@chu-montpellier.fr
Type 2 Diabetes Burnout : What is the Remedy and for Whom? Needles? Or Pump?
What is the Current Experience of Glucose Control with Insulin Injections in Type 2 Diabetes?
HbA1c (%) 9,5 9 8,5 8 7,5 7 6,5 6 Insulin Therapy in Type 2 Diabetes and Outcomes on HbA1c Abraira et al, VA CSDM, Diabetes Care, 1995, 18: 1113-23 Follow-up of intensively treated group (75 patients) 9,3 OHA+/- INS 7,9 Bedtime INS 7,4 7,4 Bedtime INS+SU p < 0.05 6,9 INS x 2/d INS x 3-4/d BASAL-BOLUS BOLUS is finally requested to reach target
140 120 Insulin 100 (IU/day) 80 Insulin Therapy in Type 2 Diabetes and Outcomes on Insulin Daily Doses Abraira et al, VA CSDM, Diabetes Care, 1995, 18: 1113-23 Follow-up of intensively treated group (75 patients, mean BMI = 30.7) 60 40 20 23 OHA +/- INS p < 0.05 61 64 Bedtime INS Bedtime INS+SU 116 INS x 2/d 133 INS x 3-4/d HIGH INSULIN DOSES are often needed to reach target
Fat Mass, Distribution and Liver Determine Necessary Insulin Doses to Reach Target Ryysy et al, Diabetes, 2000, 49: 749-58. 20 Type 2 patients insulin treated for > 1 year, HbA1c: 7.6 + 0.2% Doses: 10-176 IU/d (Bedtime NPH + metformin), Weight: 67-127 kg Correlations with insulin absorption Visceral fat (ml) -0,73 p<0,0004 SC fat (ml) -0,60 p<0,0072 BMI -0,59 p<0,006 Correlations with insulin dose to suppress endogenous glucose production Liver steatosis (%) 0,72 p<0,0013 SC fat (ml) 0,67 p<0,0065 Body fat mass (kg) 0,60 p<0,01 Insulin doses needed to reach glucose control depends on : 1) Liver steatosis (r=0,76; p<0,0004) 2) waist/hip ratio (r=0,69; p<0,0008) 3) BMI (r=0,68; p<0,0009)
% reduction of hypos Glargine vs. 1-21 2 Daily NPH in Type 2 Diabetes: Meta-Analysis Rosenstock et al, Diabetes Care, 2005 60 50 40 30 20 10 Glargine (n=1142) vs. 1-21 2 daily NPH (n=1162) HbA1c < 7% : 30,8 % vs. 32,1 % (NS) 0 Hypoglycemia Nocturnal Hypos Severe Hypos Noct. Severe Hypos P = 0.0006 P < 0.0001 P = 0.0442 P = 0.0231
[Glulisine vs. Regular Insulin] + NPH Twice Daily in Type 2 Diabetes Dailey et al, Diabetes Care, 2004 876 patients, 26 weeks follow-up HbA1c decrease from baseline (%) Post-breakfast blood glucose (mg/dl) Post-dinner blood glucose (mg/dl) Regular + NPH x 2/day 0.3 % 162 163 Glulisine + NPH x 2/day 0.46 % (p=0.0029) 156 (p<0.05) 154 (p<0.05) Hypoglycemia and weight = no difference
[NPH vs. DETEMIR] + ASPART in Type 2 Diabetes Haak et al, Diabetes Obes Metab,, 2005 505 patients, 26 weeks follow-up HbA1c decrease from baseline (%) Between-day intra-subject blood glucose variability Weight gain (kg) NPH + ASPART 0.4 % (p=0.0001) Higher + 1.80 DETEMIR + ASPART 0.2% (p=0.004) Lower (p=0.021) +1.00 (p=0.017)
[NPH+Regular]] vs. [Detemir+Aspart[ Detemir+Aspart] ] in Type 2 Diabetes Mellitus Raslova et al, Diabetes Res Clin Pract,, 2004 395 patients, 22 weeks follow-up HbA1c decrease from baseline (%) NPH + (Regular x 3/day) 0.58 Detemir + (Aspart x 3/day) 0.65 Between-day intra- suject blood glucose variability (mmol/l) Weight gain (kg) 1.54 1.13 1.20 (p<0.001) 0.51 (p = 0.038) No significant difference on hypos
Effectiveness of Inhaled Insulin Exubera TM in Type 2 Diabetes Hollander et al., Diabetes Care 2004;27:2356-62. 10 9 Mean A1c (%) 8 7 6 5 Screening Baseline 6 12 24 Duration of treatment (weeks) Inhaled insulin (n=149) SC insulin (n=149)
Exubera TM in Type 2 Diabetes: Change in Body Weight (6 Months) Hollander et al., Diabetes Care 2004;27:2356-62. 2.0 Mean weight change (kg) 1.5 1.0 0.5 0.0 Inhaled SC
Current Experience of Glucose Control with Insulin Injections in Type 2 Diabetes Evolution of insulin therapy toward basal-bolus bolus is needed to reach target. High insulin doses are commonly requested, according to fat distribution and liver steatosis. Insulin analogues decrease occurrence of hypos, improve glucose stability, may reduce weight gain but often fail in further lowering of HbA1c. Expected benefit of inhaled insulin looks minor, except for the acceptance of insulin and perhaps for weight control.
What Can We Expect from Insulin Pumps in Type 2 Diabetes?
IV Insulin Infusion Followed by One-year CSII in 8 Severely Resistant Type 2 Patients Pouwels et al, Diabetic Medicine, 2003 12 11 10 9 8 7 6 Baseline 6 months 9 months 12 months Follow-up of HbA1c using CSII for 1 year With Weight stability p < 0.0005 vs. Baseline p < 0.001 vs. Baseline Effects of 4 weeks with IV insulin infusion
Forty-week Experience with CSII in 10 Severely Obese Type 2 Patients Wainstein et al, Diabetes Care, 2001 Daily Insulin Dose (IU/kg) Weight (kg) HbA1c (%) Baseline 1.46 +/- 0.43 95.9 +/- 13.2 12.34 +/- 1.74 After 40 weeks 1.19 +/- 0.42 93.4 +/- 12.7 9.56 +/- 0.76
Does it mean that insulin pump is only good for me? No Sir, we shall perform randomized studies now!
CSII [Aspart[ Aspart] ] vs. Multiple Daily Insulin Injections [Aspart + NPH] in Type 2 Diabetes: a Randomized, Parallel-Group Group,, 24-week Study Raskin P et al, Diabetes Care 2003, 26: 2598-603. 8,2 8 HbA1c (%) 7,8 7,6 7,4 CSII MDI 7,2 7 Baseline 24 weeks P<0.05 vs. baseline
Baseline and End-of of-study Eight Point Blood Glucose Profiles (ITT) * p = 0.02
Change-from from-baseline Improvements in Patient Satisfaction Subscores at the End of Study * p<0.025 ** p<0.01 *** p<0.001
For sure, they will never try to randomize me Don t be so negative, it may happen! and for now, don t move!!
Insulin [lispro[ lispro] ] Pump Therapy vs. Multiple Daily Injections [Regular + NPH] in Obese Type 2 Diabetic Patients J Wainstein et al, Diabetic Medicine, 2005 40 Type 2 insulin-treated patients (BMI:( 30-45 45; ; HbA1c > 8.5%; insulin doses > 1 iu/kg/d; metformin), 2 x 18-week randomized cross-over over study, 12-week wash-out b/w periods, 29 completers Direct treatment effect by group, ITT analysis
The Results of this Study Favour Pump Therapy for hard-to to-control Type 2 Obese Patients Take your hands away of my pump!!! Gee! That s fun. Can I be randomized, too?
CSII [lispro[ lispro] ] vs. Multiple Daily Injections [lispro[ + glargine] ] in Adults older than 60 years Herman WH et al, Diabetes Care, 2005 107 Type 2 insulin-treated patients (Age( > 60; BMI: 32; HbA1c: 8.2%), 12-month randomized parallel study, 98 completers HbA1c (%) CSII o MDI -1 0 1 2 4 6 8 10 12 Study month No difference in weight gain, incidence of hypos, daily insulin doses, QoL indices
OK for oldies, but what about us, playing rugby? Don t look for my pump, it s internal!
) ) ) ) ) What is an Internal Insulin Pump? Sideport Titanium case (81 x 20 mm, 146 g) Catheter ter Subcutaneous Part Anchoring Flange Intraperitoneal Part MODEL SN ) ) ) ) ) Telemetry Programmer Central Port Anchoring hoops Medtronic-MiniMed MiniMed Implantable Pump, model 2007
HbA1c (%) Randomized, Controlled,, Prospective Study: : Implantable Pump vs. MDI in 122 Type 2 Patients 10 9 8 7 8,85 7,54 8,77 7,34 Saudek et al,, JAMA 1996 SD BG (mg/dl) 60 50 40 53 46 50 34,5 Weight (kg) 110 100 97,8 initial 12 months 101,4 6 30 93 92 5 MDI IMP PUMP 20 MDI IMP PUMP 90 MDI IMP PUMP p < 0,001 vs initial p < 0,01 vs MDI p < 0,001 vs MDI
What Can We Expect from Insulin Pumps in Type 2 Diabetes? Insulin pumps are usable at any age with at least similar effectiveness, no further weight gain, no more acute events when compared with MDI using analogues or not. They may provide better satisfaction because of increased flexibility of use and avoidance of injections, as they do in type 1 diabetic patients. They may help in more efficient glucose control in severely resistant, obese patients. Further studies are needed to assess cost- effectiveness and benefit.
Insulin Pump Therapy in Type 2 Diabetes Yes, when glucose control with MDI looks as an impossible mission. No, there is no reason for any diktat against pump in these patients. We will probably have to think more of using pumps in the future: younger patients, QoL issues, glucose sensors
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