Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we now turn to the some of the factors that can affect physical activity. Similar to the factors that can affect ingestive behaviour, there are a host of factors that can significantly affect physical activity:
A wide range of socio‐cultural determinants of physical activity exist. These range from factors related to the built environment (e.g. urban sprawl, walkability, street connectivity), neighbourhood safety, social networks, and public transportation to socioeconomic limitations as well as customs and beliefs that can influence vocational or recreational physical activity. For example, being promoted from a physically active outdoor job to a sedentary indoor job, moving from a dense urban location to a rural or suburban residence, immigration to a Western country, pregnancy and change in familial status or time constraints can all promote sedentariness and increase the risk of weight gain. Indentifying and addressing the socio‐cultural barriers to physical activity can be a key to successful weight management. Patients facing significant socio‐cultural barriers to activity may specifically benefit from counselling by an occupational and/or recreational therapist.
Numerous medical conditions can lead to a reduction in or inability to engage in physical activity. These include musculoskeletal pain or immobility resulting from injury, osteoarthritis or fibromyalgia as well as any other condition that can affect physical performance such as cardiorespiratory disease, obstructive sleep apnoea, chronic fatigue, stroke or urinary incontinence. Alleviating these factors and thereby reducing immobility may be the first step in addressing weight management in these patients. Given the predominant role of musculoskeletal disorders and pain as a barrier to mobility and physical activity, these patients may benefit most from physiotherapeutic interventions and pain management.
Psychological factors and mental health
Lack of motivation, low energy levels and disinterest in exercise (especially in a previously active individual) can be a symptom of depression. Social anxiety disorder, agarophobia, sleep disorders or substance abuse can all affect physical activity levels. Body image issues and self‐efficacy can likewise pose important psychological barriers that may require specific professional counselling and intervention to promote a more active lifestyle.
Although published research on this issue is limited, it is reasonable to assume that medications, which reduce energy levels, promote drowsiness, impair coordination or limit cardiorespiratory function can pose significant barriers to physical activity.
Now that we have discussed why it is important to asses the many factors that can affect energy metabolism, ingestive behaviour, and physical activity, in coming posts, we can explore how to apply this framework to patients presenting with weight gain.
Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we now turn to the some of the factors that can affect ingestive behaviour, this post focusses on medications:
Medications and Drugs That Affect Hunger and Appetite
A wide range of medications and illicit drugs can promote hunger and appetite. These include some oral anti‐diabetic agents, antidepressants, atypical antipsychotics, anticonvulsants, certain hormonal preparations including corticosteroids and oral contraceptives, as well as the medicinal and recreational use of marihuana. Alcohol and other mind‐altering drugs can also promote over‐eating by increasing appetite, reducing dietary restraint and promoting disinhibition. Patients presenting with weight gain and obesity need a careful review of their medication and substance abuse history.
Commentary: Obviously this a complex topic as the number of medications and recreational substances that can affect appetite and eating behaviour is long. Nevertheless, assessing the possibility that a change in appetite and weight gain are due to this factor is an essential part of clinical assessment.
Liraglutide Effects on Upper Gastrointestinal Investigations: Implications Prior to Bariatric Surgery
With the considerable waits that patients in Canada often face prior to bariatric surgery, we generally recommend that patients, who have access to them, try anti-obesity medications while waiting. This not only prevents further wait gain, but also often helps them shed a significant amount of weight prior to surgery.
The GLP-1 analogue liraglutide is now approved for long-term obesity treatment and is generally well tolerated. Nevertheless, we now present a series of patients in Obesity Surgery, who were treated with liraglutide 3.0 mg whilst waiting for bariatric surgery, and showed significant upper GI dismotility that was reversible on discontinuation of liraglutide.
Although, investigations of upper GI motility are by no means part of routine assessment for bariatric surgery, tests may be ordered in patients who present with unclear upper GI symptoms, as the findings may guide the choice of surgical intervention.
In this paper, we present six cases in which patients treated with liraglutie 3.0 mg presented with varying degrees of esophageal and/or gastric dysmotility demonstrated using a variety of investigative procedures including formal gastric emptying scintiography as well as less specific esophageal manometry, and upper endoscopy.
In all cases normal motility was restored on discontinuation of liraglutide and all patients subsequently underwent or are continuing to wait for bariatric surgery.
Based on our observations we discuss that,
“Liraglutide is associated with decreased esophageal peristalsis and gastric emptying. These effects can result in abnormal upper GI investigations, leading to delays, increased testing, and questions of patient candidacy for surgery. If patients on liraglutide are noted to have abnormal esophageal manometry or gastric emptying studies, medication should be discontinued, with repeat studies done to look for reversibility. If this abnormal result is due to drug effect, this should not preclude patients from having bariatric surgery.”
Just how long liraglutide needs to be stopped prior to performing upper GI investigations remains unclear. Furthermore, as the dysmotility often appears to be symptomless and well-tolerated, we do not recommend routine ordering of motility tests in patients treated with liraglutide.
Disclaimer: I have served as a consultant and speaker for Novo Nordisk, the makers of liraglutide.
Readers will recall, that once-weekly injections of the novel long-acting GLP-1 analogue semaglutide was recently shown (in patients with type 2 diabetes) to result in a rather impressive weight loss.
Now, a phase II dose-finding study comparing various oral doses of semaglutide to subcutaneous injections in patients with type 2 diabetes was just published in JAMA.
The 26-week trial with 5-week follow-up included around 600 patients with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized to once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks.
Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%);
Significant reductions were also seen in body weight with both oral (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg)>
Adverse events (largely consisting of mild to moderate gastrointestinal events) were as expected and relatively comparable between the treatment arms.
Although this was a diabetes study, these findings clearly hold promise for the further development of an oral formulation of semaglutide for the obesity indication.
Disclaimer: I have served as a consultant for Novo Nordisk, the maker of semaglutide.
Readers may by now be familiar with the GLP-1 analogue liraglutide, which has now been approved at the 3 mg dose (Saxenda(R)) for long-term obesity treatment in a growing number of countries.
Now, Novo Nordisk, the maker of liraglutide, announced preliminary results from their long-acting GLP-1 analogue semaglutide, suggesting a rather remarkable ~14% weight loss in a one-year double-blind placebo controlled dose-finding study.
According to the company’s press release,
In the trial, 957 people with obesity were randomised to treatment with doses of semaglutide between 0.05 to 0.4 mg/day or placebo. Liraglutide 3.0 mg/day was included for comparison. Approximately 100 people were included in each active treatment arm in combination with diet and exercise. All people in the trial were treated for 52 weeks followed by a 7-week follow-up period.
From a mean baseline weight of around 111 kg and a body mass index of approximately 39 kg/m2, a weight loss up to 17.8 kg was observed after 52 weeks of treatment with semaglutide. This corresponded to an estimated 13.8% weight loss compared to the weight loss of 2.3% achieved by diet, exercise and placebo alone, with all treatment arms adjusted for people discontinuing treatment in the study. The results from the liraglutide 3.0 mg treatment arm were broadly in line with previously reported data.
Side effects were mainly reported as gastro-intestinal, as expected from this class of hormone analogues.
Clearly, if borne out by the final publication and confirmed in larger and longer studies, semaglutide may well prove to be even more effective than liraglutide.
It may be worth noting, that the ~14% weight loss reported in this trial comes very close to the mean ~15% weight loss seen with adjustable gastric banding, a bariatric surgical technique that is now increasingly seen as obsolete due to long-term complications and loss of effectiveness.
I’m guessing it’s now on to Phase 3 for this promising anti-obesity drug.
Disclaimer: I have received speaking and consulting honoraria from Novo Nordisk, the maker of liraglutide and semaglutide