Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk

Figures & data

Table 1 Summary characteristics of amylin and pramlintide

Amylin

37 amino acid compound

Co-secreted with insulin from beta cells

Deficient in type 1 and type 2 DM

Renal clearance

Physiological effects Suppression of endogenous glucagon production (especially in the postprandial state) Reduction in postprandial hepatic glucose production Reduction in gastric emptying time Centrally mediated induction of satiety Reduction in postprandial glucose levels

Pramlintide

Synthetic analogue of amylin (3 amino acid substitutions with proline for

native amino acids

Subcutaneous administration

Effects in type 1 and type 2 DM Reduction in prandial glucose Reduction in HgbA1c Reduction in prandial glucagons Slowed gastric emptying Weight loss

Table 2 Studies of pramlintide use in patients with type 1 DM

Study	Patients (n)	Study design	Duration (weeks)	Pramlintide dose	HbA1c Δ(%)	Wt (kg)
(Fineman et al 1999a)	586	DB, PC, multicenter	26	60 μg tid or 90 μg bid-tid or placebo	−0.2 (p = sign.) −0.1 (NS) −0.1 (NS) +0.1	−1.6 −0.7 −1.6 +0.3 (NS)
(Gottlieb 2000)	479	DB, PC, multicenter	52	60 μg tid-qid or placebo	−0.4/−0.3 NR (p = sign.)	−1.4/−1.7 NR (p = sign.)
(Whitehouse 2002)	480	DB, PC, multicenter	52	30−60 μg qid or placebo	−0.39 −0.12 (p = 0.0071)	−0.5a +1.0a (p < 0.001)
(Ratner et al 2004)	479	DB, PC, multicenter	52	60 μg tid-qid or placebo	−0.29/−0.34 −0.04 (p < 0.011 and <0.001)	−0.4/−0.4 +0.8 (p < 0.027 and <0.040)
(Edelman et al 2006)	296	DB, PC, multicenter	29	30–60 μg tid or placebo	−0.5 −0.5	−1.3 +1.2 (p < 0.0001)

a These data were extrapolated from graphs, because the absolute values were not reported in the test of the published studies.

Note: Fineman 1999, Whitehouse 2002, Ratner 2004 studies − subjects with entry HbA1c between 7.0 and 8.5% (n = 477) are summarized in Ratner et al 2005.

Abbreviations: DB, double-blind; MC, multicenter; PC, placebo-controlled; R, randomized; RCT, randomized control trials.

Table 3 Studies of pramlintide use in patients with type 2 DM

Study	Pat (n)	Study design	Duration (weeks)	Pramlintide dose	ΔHbA1c (%)	ΔWeight (kg)
(Thompson et al 1998)	203	MC, R, DB, PC	4	Placebo	−0.27	−0.04
				30 μg qid	−0.53*	−0.36
				60 μg tid	−0.58*	−0.89**
				60 μg qid	−0.51*	−0.72**
(Gottlieb et al 2007)	499	MC, DB, PC	26	Placebo	−0.1	0.1
				90 μg bid	−0.3	−0.8
				90 μg tid	−0.4	−1.3
				120 μg bid	−0.4*	−1.4
(Ratner et al 2005)	538	MC, R, DB, PC	52	Placebo	−0.2c	1.0c
				30 μg tid	−0.3c	−0.3c
				75 μg tid	−0.5c	−0.4*c
				150 μg td	−0.6*,c	−1.2*c
(Hollander et al 2003b)a	656	MC, R, DB, PC	52	Placebo	−0.25c	+0.7
				60 μg tid	− b	−b
				90 μg bid	−0.35	−0.5
				120 μg bid	−0.62*	−1.4*
(Hollander et al 2004)	498	Post hoc analysis of 2 RCTd	26	Placebo 120 μg bid	−0.41***	−1.8***

a Subset of this population with lower HbA1c values also published (Hollander et al 2003a).

b Excluded after efficacy analyses after results from another study (not identified) indicated that this dose was less effective.

c These data were extrapolated from graphs, because the absolute values were not reported in the test of the published studies.

d Gottlieb et al (1999), Hollander et al (2004).

* p < 0.05;

** p < 0.01;

*** p < 0.0001.

Abbreviations: DB, double-blind; MC, multicenter; PC, placebo-controlled; R, randomized; RCT, randomized control trials.

Figure 1 Mean percent changes in lipid values in 203 type 2 diabetic patients on placebo and 3 different doses of pramlintide for 4 weeks. Derived from Thompson et al (1998).

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