ObjectivesTo determine the effect on weight of two Mobile technology-based (mHealth) behavioral weight loss interventions in young adults.MethodsRandomized, controlled comparative effectiveness trial in 18–35 year olds with BMI ≥ 25 kg/m2 (overweight/obese), with participants randomized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone (CP); personal coaching enhanced by smartphone self-monitoring (PC); or Control.ResultsThe 365 randomized participants had mean baseline BMI of 35 kg/m2. Final weight was measured in 86% of participants. CP was not superior to Control at any measurement point. PC participants lost significantly more weight than Controls at 6 months (net effect −1.92 kg [CI −3.17, −0.67], p=0.003), but not at 12 and 24 months.ConclusionsDespite high intervention engagement and study retention, the inclusion of behavioral principles and tools in both interventions, and weight loss in all treatment groups, CP did not lead to weight loss and PC did not lead to sustained weight loss relative to control. Although mHealth solutions offer broad dissemination and scalability, the CITY results sound a cautionary note concerning intervention delivery by mobile applications. Effective intervention may require the efficiency of mobile technology, the social support and human interaction of personal coaching, and an adaptive approach to intervention design.Trial RegistrationClinicalTrials.gov Identifier NCT01092364.https://clinicaltrials.gov/ct2/show/NCT01092364?term=Cell+phone+intervention+for+you&rank=3

About 40% of the therapeutic agents in use today exert their effects through seven-transmembrane receptors (7TMRs). When activated by ligands, these receptors trigger two pathways that independently transduce signals to the cell: one through heterotrimeric GTP-binding proteins (G proteins) and one through β-arrestins; so-called biased agonists can selectively activate these distinct pathways. Here, we investigate selective activation of these pathways through the use of a biased agonist for the type 1 parathyroid hormone (PTH)-PTH-related protein receptor (PTH1R), (DTrp 12 , Tyr 34 )-PTH(7-34) (PTH-βarr), which activates β-arrestin but not classic G protein signaling. In mice, PTH-βarr induces anabolic bone formation, as does the nonselective agonist PTH (1-34), which activates both mechanisms. In β-arrestin2-null mice, the increase in bone mineral density evoked by PTH(1-34) is attenuated and that stimulated by PTH-βarr is ablated. The β-arrestin2-dependent pathway contributes primarily to trabecular bone formation and does not stimulate bone resorption. These results show that a biased agonist selective for the β-arrestin pathway can elicit a response in vivo distinct from that elicited by nonselective agonists. Ligands with these properties may form the basis for improved 7TMR-directed pharmacologic agents with enhanced therapeutic specificity.