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Pml5.0
Pramlintide – Forschung
Überwiegend Mechanismus / Beobachtung
11 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Pramlintide sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus hochwertigen Meta-Analysen und randomisierten Studien, veröffentlicht 2002–2017 mit einer typischen Studiengröße von 411 Teilnehmenden.
Basierend auf 11 Studien · 2 Meta-Analysen · 8 RCTs · 2,567 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Blood sugar & glycemic controlPlacebo-korrigierte HbA1c-Senkungen von ~0,3-0,5 % als Ergänzung zum Mahlzeiten-Insulin, anhaltend bis 52 Wochen; dämpft postprandiale Glukose deutlich · Wochen bis 6-12 Monate
Überwiegend Mechanismus / Beobachtung10 Studien
Weight managementAssoziiert mit Gewichtsverlust (~1-2,6 kg als Diabetes-Ergänzung; ~6-7 kg über 12 Monate bei Adipositas) statt Gewichtszunahme · Monate
Überwiegend Mechanismus / Beobachtung10 Studien
Safety & adverse effects
Überwiegend Mechanismus / Beobachtung10 Studien
Ältere Forschungsbasis
Neueste Studie von 2017 · Neueste Meta-Analyse: 2017
200220092017
1RCTn=651 · large study2004
Addition of pramlintide [60 µg three times daily (TID) or four times daily (QID)] to insulin led to significant reductions in HbA(1c) from baseline to Week 52 of 0.29% (P < 0.011) and 0.34% (P < 0.001), respectively, compared with a 0.04% reduction in placebo group.
Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG. · Diabet Med (2004)
Double-blind, placebo-controlled, parallel-group phase-3 RCT in 651 patients with type 1 diabetes, mealtime pramlintide vs placebo added to insulin for 52 weeks
Placebo-corrected HbA1c reduction ~0.3% sustained to week 52; ~3× the proportion of pramlintide vs placebo patients reached HbA1c <7%
Achieved without increased insulin use, and with a ~0.4 kg weight loss vs a 0.8 kg gain on placebo
Treatment with pramlintide 120 µg BID led to a sustained reduction from baseline in HbA(1c) (-0.68 and -0.62% at weeks 26 and 52, respectively)... accompanied by a mean weight loss (-1.4 kg vs. +0.7 kg with placebo at week 52, P < 0.05) and occurred without an overall increase in the severe hypoglycemia event rate.
Hollander PA, Levy P, Fineman MS, Maggs DG, Shen LZ, Strobel SA, Weyer C, Kolterman OG. · Diabetes Care (2003)
52-week double-blind, placebo-controlled, parallel-group phase-3 RCT in 656 insulin-treated patients with type 2 diabetes
Pramlintide 120 µg BID reduced HbA1c by 0.62% at 52 weeks, significantly more than placebo; ~2× as many patients reached HbA1c <8% (46% vs 28%)
Mean weight loss -1.4 kg vs +0.7 kg gain on placebo at week 52, with no overall rise in severe hypoglycemia
Mealtime pramlintide treatment as an adjunct to insulin improved long-term glycemic control without inducing weight gain or increasing the overall risk of severe hypoglycemia in patients with type 1 diabetes.
Whitehouse F, Kruger DF, Fineman M, Shen L, Ruggles JA, Maggs DG, Weyer C, Kolterman OG. · Diabetes Care (2002)
52-week double-blind, placebo-controlled RCT in 480 patients with type 1 diabetes, 30 µg pramlintide QID vs placebo added to insulin, plus a 1-year open-label extension
HbA1c fell 0.67% from baseline to week 13, significantly more than placebo (0.16%; P<0.0001); a placebo-corrected difference was sustained through week 52
Glycemic benefit was associated with weight loss rather than weight gain and no increase in the overall severe-hypoglycemia event rate
Reductions in A1C (-0.70 ± 0.11% vs. -0.36 ± 0.08%; P < 0.05) and PPG increments... were greater in pramlintide- versus placebo-treated patients... Glycemic improvements were accompanied by progressive weight loss with pramlintide and weight gain with placebo (-1.6 ± 0.3 kg vs. +0.7 ± 0.3 kg; P < 0.0001).
Riddle M, Frias J, Zhang B, Maier H, Brown C, Lutz K, Kolterman O. · Diabetes Care (2007)
16-week double-blind, placebo-controlled RCT in 212 patients with type 2 diabetes on insulin glargine ± oral agents
More pramlintide than placebo patients reached a composite control endpoint (25% vs 7%; P<0.001)
Greater HbA1c reduction (-0.70% vs -0.36%) and lower postprandial glucose increments
In patients taking basal insulin and OADs, premeal fixed-dose pramlintide improved glycemic control as effectively as titrated RAIAs. The pramlintide regimen sometimes caused nausea but no weight gain and less hypoglycemia.
Riddle M, Pencek R, Charenkavanich S, Lutz K, Wilhelm K, Porter L. · Diabetes Care (2009)
24-week open-label RCT in 113 patients with type 2 diabetes, mealtime pramlintide 120 µg vs a titrated rapid-acting insulin analog added to basal insulin
More pramlintide patients reached A1C ≤7.0% without weight gain or severe hypoglycemia (30% vs 11%; P=0.018); similar A1C reductions overall
Rapid-acting insulin caused weight gain (+4.7 kg) while pramlintide did not (+0.0 kg; P<0.0001)
Placebo-corrected weight loss with 120 µg t.i.d. and 360 µg b.i.d. averaged... 6.1 ± 2.1 kg (5.6 ± 2.1% body wt) and 7.2 ± 2.3 kg (6.8 ± 2.3% body wt), respectively, at month 12... 40 and 43% of subjects... achieved ≥10% weight loss (vs. 12% for placebo).
Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C. · Diabetes Care (2008)
Double-blind, placebo-controlled, dose-ranging RCT in 411 obese subjects WITHOUT diabetes, pramlintide plus structured lifestyle intervention, with a single-blind extension to 12 months
Placebo-corrected weight loss ~6-7 kg (~5.6-6.8% body weight) at month 12 in effective dosing arms; initial loss was regained on placebo
40-43% of pramlintide subjects achieved ≥10% weight loss vs 12% on placebo
Pramlintide significantly reduced haemoglobin A1c (HbA1c) (-0.33% [95% CI -0.51, -0.14], p = 0.004) and weight (-2.57 kg, [95% CI -3.44, -1.70], p < 0.00001) versus the control group... patients randomized to pramlintide were 1.8 times more likely to report nausea of any severity versus control.
Singh-Franco D, Perez A, Harrington C. · Diabetes Obes Metab (2011)
Meta-analysis of 8 RCTs (four type-2-diabetes trials, N=930; four obesity trials, N=686)
Small HbA1c reduction (-0.33%) and modest weight loss (-2.57 kg) vs control; -2.27 kg weight loss in obese subjects without diabetes
No increase in hypoglycemia of any severity overall, but ~1.8× more nausea
Pramlintide was somewhat more effective than placebo as adjunct therapy for improving HbA(1c) levels and weight in adults with type 1 diabetes on conventional insulin therapy, or type 2 diabetes... with between-group differences in HbA(1c) levels in the range of 0.2% to 0.4%.
Lee NJ, Norris SL, Thakurta S. · Ann Fam Med (2010)
Systematic review of RCTs (3 in type 1 diabetes, 4 in type 2 diabetes; all in adults, none longer than 52 weeks)
Between-group HbA1c differences modest (~0.2-0.4%); benefit clearer with conventional than with intensive insulin therapy
Weight loss with pramlintide vs weight gain with placebo across both diabetes types
After 4 weeks on pramlintide, postprandial glucose, glucagon, and triglyceride excursions were reduced by approximately 86, approximately 87, and approximately 72%, respectively (incremental areas under the curve, all P < 0.05 vs. baseline).
Levetan C, Want LL, Weyer C, Strobel SA, Crean J, Wang Y, Maggs DG, Kolterman OG, Chandran M, Mudaliar SR, Henry RR. · Diabetes Care (2003)
Mechanistic RCT in 18 patients with type 1 diabetes on continuous subcutaneous insulin infusion, 30 µg pramlintide TID for 4 weeks
Large reductions in postprandial glucose (~86%), glucagon (~87%) and triglyceride (~72%) excursions
Shifted 24-h glucose toward the euglycemic range with a ~17% reduction in mealtime insulin and no severe hypoglycemia
Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Δ-202 ± 64 kcal, -23 ± 8%, p<0.01) and obese (Δ-170 ± 68 kcal, -16 ± 6%, p<0.02) groups, without affecting meal duration.
Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Strobel S, Wang Y, Burns C, Lush C, Weyer C, Horowitz M. · Diabetologia (2005)
Randomized, double-blind, placebo-controlled crossover meal-test study in 11 insulin-treated men with type 2 diabetes and 15 non-diabetic obese men
A single 120 µg pramlintide injection cut ad libitum energy intake by ~16-23% vs placebo
Hunger and gut-peptide profiles indicated a primary satiogenic effect independent of other anorexigenic gut peptides