Clinical trials will be needed to test whether drugs that inhibit PTP1B and thereby increase the amplitude of leptin signaling have a meaningful impact on body weight, either in people with obesity (which may be characterized by a degree of leptin resistance (67)) or in people in the weight-reduced state, where relative leptin deficiency is a major driver of weight regain (68, 69). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.