Once Weekly GLP-1 in Persons With Spinal Cord Injury
Condition: Spinal Cord Injuries; Insulin Resistance; Pre Diabetes; Obesity
MeSH terms: Spinal Cord Injuries; Insulin Resistance; Prediabetic State
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic spinal cord injury (SCI) results in adverse soft tissue body composition changes and
      an extremely sedentary lifestyle. These abrupt changes often lead to a high prevalence of
      cardiometabolic diseases, such as impaired glucose tolerance/diabetes mellitus and
      dyslipidemia, conditions which predispose those with SCI to an increased risk for
      cardiovascular disease compared to the general population. Due to paralysis and wheel chair
      dependence, maintaining an adequate level of physical activity to counteract these
      deleterious metabolic changes presents a unique obstacle because conventional first line
      interventions are lifestyle modifications (e.g., diet and exercise), which may be difficult
      to achieve. Recently, a new medication has been approved by the Food and Drug Administration
      to improve glycemic control in individuals with diabetes mellitus, and it has also been
      investigated as an off-label treatment to induce weight loss. Glucagon-like peptide-1 (GLP-1)
      agonists are a class of drugs designed to mimic the endogenous incretin hormones released
      from the gut in a glucose dependent manner following a meal. The mechanisms of action for
      this drug class of medications include stimulation of glucose-dependent insulin secretion,
      inhibiting glucagon release, slowed gastric emptying, and reduction of postprandial glucose
      excursions following food intake. In addition to improved glycemic control, this class of
      medications also shows promise for its non-glycemic action of facilitating weight loss. The
      method of delivery of the GLP-1's is by self-administered injections once daily or once
      weekly, depending on the severity of the clinical case and therapeutic targets for a specific
      patient.
    

Detailed description: 
      Obesity is an underlying condition that predisposes to the development of several medical
      disorders and diseases. It is well appreciated that obesity has reached pandemic proportions
      in Western societies. The World Health Organization (WHO) estimates that 1.9 billion adults
      worldwide are overweight and 600 million of these individuals are further sub-classified as
      obese, with a 44% estimated burden for type 2 diabetes mellitus (T2DM) being attributed to
      being overweight/obese, as well as a 23% estimated burden for heart disease ("Obesity and
      overweight," 2016). Excess adipose tissue is assumed to play an integral role in the
      pathogenesis of vascular dysfunction and the development of T2DM (Lau, Dhillon, Yan, Szmitko,
      & Verma, 2005).

      During the acute and chronic phases of SCI, marked adverse changes occur in soft tissue body
      composition and associated carbohydrate and lipid metabolism. After an initial rapid loss of
      lean tissue below the neurological level of injury, a more insidious and progressive lean
      tissue loss is observed (Modlesky et al., 2004; Spungen et al., 2003), which is accompanied
      by an increased total body adiposity (Spungen et al., 2003), with accumulation of fat in the
      abdominal (e.g., visceral) compartment (Gorgey, Mather, Poarch, & Gater, 2011). These adverse
      changes to body composition contribute to, and are associated with, a higher prevalence of
      insulin resistance and disorders of carbohydrate metabolism (e.g., impaired glucose tolerance
      and T2DM) than that reported in the general population (Bauman & Spungen, 1994). The primary
      approach to treat T2DM in the general population is diet and exercise (i.e., lifestyle
      modification). Of note, the profound inactivity and adverse soft tissue body composition
      changes that occur in individuals after SCI result in metabolic morbidity which is extremely
      difficult to manage with lifestyle modification alone. Conventional therapeutic strategies
      employed in the adjunctive treatment of carbohydrate metabolism disorders in the general
      population include several pharmacological approaches to maintain and improve glycemic
      control are in standard practice and include reducing the serum glucose concentration (i.e.,
      insulin, sulphonylureas, thiazolidinediones or glitazones), suppressing hepatic
      gluconeogenesis (i.e., insulin, biguanides), stimulating endogenous insulin secretion (i.e.,
      sulphonylureas), and/or by inhibiting glucose renal reabsorption and increasing glycosuria
      (i.e., SGLT-2 inhibitors).

      In 2005 a new class of drugs was approved for the treatment for T2DM by targeting the GLP-1
      receptor. Exenatide is a GLP-1 agonist that acts as an incretin hormone, and it belongs to a
      class of gastrointestinal hormones which are released from the L cells of the intestines in
      response to food ingestion that, as one of its mechanisms of action, increase insulin
      secretion from pancreatic beta cells (Vilsboll et al., 2003). This phenomenon that was coined
      "the incretin effect" in the 1960's described the significantly higher plasma insulin levels
      following orally versus intravenously administered glucose, which can account for 50 to 70%
      of the insulin secretion observed after food intake (Baggio & Drucker, 2007). Treatment with
      GLP-1's has increased over the past several years because of their mechanism of action to
      increase insulin secretion, inhibit glucagon release in a glucose-dependent manner, thus
      minimizing the risk for hypoglycemia (Baggio & Drucker, 2007; Nauck, Stockmann, Ebert, &
      Creutzfeldt, 1986; Vilsboll, Krarup, Madsbad, & Holst, 2002). Numerous multi-ethnic and
      multi-national trials have been performed with exenatide, but none have been reported in
      persons with SCI. Previous investigation with exenatide once-weekly in able-bodied
      individuals has resulted in weight loss ranging from 1.6 to 3.9 kg following 24 weeks of
      intervention (Bergenstal et al., 2010; Blevins et al., 2011; Buse et al., 2013; Chiquette,
      Toth, Ramirez, Cobble, & Chilton, 2012; Davies et al., 2013; Diamant et al., 2010; Drucker et
      al., 2008; Inagaki, Atsumi, Oura, Saito, & Imaoka, 2012; Ji et al., 2013; Russell-Jones et
      al., 2012). As such, to date there is no evidence of the potential efficacy of exenatide to
      result in weight loss, improve glycemic control, and/or reduce insulin resistance in persons
      with SCI.
    

Intervention name(s): Semaglutide 1MG Injection [Ozempic]; No Intervention
Intervention type(s): Drug; Other
Intervention description(s): Once weekly injection of 1mg of Semaglutide.; No injection will be administered
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Glucagon-Like Peptide-1