Exenatide once-weekly (EQW [2 mg s.c.]) is under development as monotherapy as an adjunct to diet and exercise or as a combination therapy with an oral antidiabetes drug(s) in adults with type 2 diabetes. This longacting formulation contains the active ingredient of the original exenatide twice-daily (EBID) formulation encapsulated in 0.06-mm-diameter microspheres of medical-grade poly-(d,l-lactide-co-glycolide) (PLG). After mechanical suspension and subcutaneous injection by the patient, EQW microspheres hydrate in situ and adhere to one another to form an amalgam. A small amount of loosely bound surface exenatide, typically less than 1%, releases in the first few hours, whereas drug located in deeper interstices diffuses out more slowly (time to maximum, *2 weeks). Fully encapsulated exenatide (i.e., drug initially inaccessible to diffusion) releases over a still longer period (time to maximum, *7 weeks) as the PLG matrix hydrolyzes into lactic acid and glycolic acid, which are subsequently eliminated as carbon dioxide and water. For EQW, plasma exenatide concentrations reach the therapeutic range by 2 weeks and steady state by 6-7 weeks. This gradual approach to steady state seems to improve tolerability, as nausea is less frequent with EQW than EBID. EQW administrations may be associated with palpable skin nodules that generally resolve without further medical intervention. In comparative trials, EQW improved hemoglobin A1c more than EBID, sitagliptin, pioglitazone, or insulin glargine and reduced fasting plasma glucose more than EBID. Weight loss due to EQW or EBID was similar. EQW is the first glucose-lowering agent that is administered once weekly.

Synthetic human pulmonary surfactant-associated protein SP-B has been interacted with chain-perdeuterated dipalmitoylphosphatidylcholine (DPPC-d62) in aqueous dispersions, and the dispersions were investigated by magnetic resonance spectroscopy. The protein caused only small perturbations of the deuterium magnetic resonance spectra in the gel and liquid-crystal states. In an amount of 11% by weight in DPPC, it produced a small reduction in the magnitude of the first moments of the spectra in the gel and a small increase (approximately 5%) in their magnitude in the liquid crystal. In the liquid crystal the protein was observed to cause a similar effect on all portions of the acyl chain, as observed by its proportional shifting of splittings obtained from "dePaked" spectra. Using data from circular dichroism spectra, the protein was found to be about 45% alpha-helical in methanol and in DPPC dispersions. alpha-Helical content was not significantly changed by the presence of 2 mM calcium or by the packing state of the acyl chains. The presence of the protein enhanced the adsorption rate of lipid into the air-water interface when dispersions of lipids or lipid plus SP-B were injected below the interface. The results could be consistent with the protein interacting with the lipid near the head groups or arranging itself around the edges of bilayer discs, or a combination of the two orientations.

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