Gut-targeted therapies for type 2 diabetes mellitus: A review

Table 1 Representative implanted electronic devices in the intestine for the treatment of type 2 diabetes mellitus

Patent/product name	The main ways to exert curative effect	Core functional/structural features	Ref.
Electroporation for obesity or diabetes treatment	Cause weight loss or control diabetes by reducing the caloric absorption by increasing levels of gut hormones important in appetite regulation and insulin secretion, and/or by reshaping the mucosa of the small intestine	The device can provide an electroporation treatment to modulate the duodenal mucosa, which can also be advanced over a guide wire under endoscopic and/or fluoroscopic guidance	[9]
Devices and methods for endolumenal gastrointestinal bypass	The devices can mimic a Roux-en-Y gastric bypass by effectively reducing stomach volume, bypassing a portion of the stomach and/or small intestine, reducing nutrient absorption in the stomach and/or small intestine	The device can be utilized to support a variety of devices which may be desirably positioned within the stomach or elsewhere in the gastrointestinal system	[10]
Methods and systems for glucose regulation	Up-regulation or down-regulation of various nerves, such as the vagus and its branches. The splanchnic nerve is used to modify the production of GLP-1 and GIP, thereby controlling glucose levels	Applying a neural conduction block to a target nerve at a blocking site with the neural conduction block selected to at least partially block nerve pulses	[11]
Treatments for diabetes mellitus and obesity	The stimulation by high-frequency alternating current is selective in blocking slow-conducting, unmyelinated C-fibers, such as those of nociceptive neurons, while minimizing effects on fast-conducting myelinated A-fibers	The ablation may be mechanical, electrical, thermal, radiative, or chemical ablation and may in some cases target a sensory nerve. In highly preferred embodiments, the ablation is a pulsed radiofrequency ablation	[12]
Methods and systems for blocking neural activity in an organ of a subject, preferably in the small intestine or the duodenum	In preferred embodiments, the invention is directed at endoluminal interventions that block, modulate and/or impact neurohormonal and other signals triggered by food passing through the gastrointestinal tract	Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using lasers, the beam being directed along or through a flexible conduit, e.g. an optical fiber	[13]

GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent insulinotropic polypeptide.

Table 2 Representative treatment of type 2 diabetes mellitus with intestinal microflora intervention

Name of the patent	Description	Ref.
Methods and compositions for microbial treatment and diagnosis of disorders	Akkermansia muciniphila, Bifidobacterium adolescentis, Clostridium acetobutylicum, from Roseburia intestinalis and the group consisting of any combination Species communities containing one or more microorganisms can be used to treat obesity or metabolic disorders such as T2DM	[32]
Methods and compositions relating to microbial treatment and diagnosis of disorders	The method comprising: Administering a therapeutically-effective amount of a pharmaceutical composition comprising a population of isolated and purified microbes, wherein at least one of said microbes comprises a microbe that encodes for an enzyme selected from the group consisting of: Butyrate kinase, butyrate coenzyme A, butyrate coenzyme A transferase, and any combination thereof, and a pharmaceutically-acceptable carrier	[33]
Methods and compositions for treatment of microbiome-associated disorders	Methods and compositions for modulating short chain fatty acid production in a subject that increase production of butyrate in said subject. The population of isolated and purified microbes comprises a microbe that modulates neurotransmitter production in the subject	[34]
Bacteria engineered to treat metabolic diseases	The engineered bacteria comprise one or more gene(s) or gene cassette(s), for the production of molecules which, inter alia, act as metabolic and/or satiety effectors and/or modulators of the inflammatory status and/or are able to convert excess bile salts into non-toxic molecules	[35]

T2DM: Type 2 diabetes mellitus.