Linaclotide for treatment of constipation - minimally absorbed peptide agonist of guanylate cyclase C receptor

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. It consists of 14 amino acids. The sequence is:

H–Cys1–Cys2–Glu3–Tyr4–Cys5–Cys6–Asn7–Pro8–Ala9–Cys10–Thr11–Gly12–Cys13–Tyr14–OH

Two randomized, 12-week trials included 1,300 patients with chronic constipation (NEJM, 2011). Patients received either placebo or linaclotide once daily for 12 weeks.

The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in linaclotide groups.

Linaclotide reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks of linaclotide in chronic constipation.

References:

Two Randomized Trials of Linaclotide for Chronic Constipation. N Engl J Med 2011; 365:527-536August 11, 2011.

Image source: Colon (anatomy), Wikipedia, public domain.

Vitamin D receptor activation with paricalcitol decreases albuminuria in type 2 diabetes

Vitamin D is a steroid hormone and a component of a complex endocrine pathway sometimes called 'vitamin D endocrine system' (Medscape, 2012).  Despite treatment with renin—angiotensin—aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria.

281 patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were enrolled in this study.

Patients were assigned to receive 24 weeks' treatment with:

- placebo
- 1 μg/day paricalcitol
- 2 μg/day paricalcitol

Paricalcitol (trade name Zemplar, Abbott Laboratories) is an analog of calcitriol, the active form of vitamin D.

The primary endpoint was the percentage change in mean urinary albumin-to-creatinine ratio (UACR).

The change in urinary albumin-to-creatinine ratio (UACR) was: −14% in the 1 μg paricalcitol group, and −20% in the 2 μg paricalcitol group.

The addition of 2 μg/day paricalcitol to RAAS inhibition safely lowers albuminuria in patients with diabetic nephropathy, and could be a novel approach to lower renal risk in diabetes.

References:
Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. The Lancet, Volume 376, Issue 9752, Pages 1543 - 1551, 6 November 2010.

Image source: Paricalcitol, Wikipedia, public domain.